VCV000294490.51 - ClinVar

NM_000186.4(CFH):c.1204C>T (p.His402Tyr)

Germline

Classification

criteria provided, conflicting classifications. Learn more about how ClinVar calculates review status.

Conflicting classifications of pathogenicity
Uncertain significance(1); Benign(15)

16 out of 16 submissions contributed to this classification

The aggregate germline classification for this variant, typically for a monogenic or Mendelian disorder as in the ACMG/AMP guidelines, or for response to a drug. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the aggregate classification.

Somatic

No data submitted for somatic clinical impact

Somatic

No data submitted for oncogenicity

Variant Details

Identifiers

NM_000186.4(CFH):c.1204C>T (p.His402Tyr)

Variation ID: 294490 Accession: VCV000294490.51

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 1q31.3 1: 196690107 (GRCh38) [ NCBI UCSC ] 1: 196659237 (GRCh37) [ NCBI UCSC ]

Timeline in ClinVar

	First in ClinVar Help The date this variant first appeared in ClinVar with each type of classification.	Last submission Help The date of the most recent submission for each type of classification for this variant.	Last evaluated Help The most recent date that a submitter evaluated this variant for each type of classification.
Germline	Dec 6, 2016	Apr 25, 2026	Feb 4, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_000186.4:c.1204C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_000177.2:p.His402Tyr	missense
NM_001014975.3:c.1204C>T	NP_001014975.1:p.His402Tyr	missense
NC_000001.11:g.196690107C>T
NC_000001.10:g.196659237C>T
NG_007259.1:g.43097C>T
LRG_47:g.43097C>T
LRG_47t1:c.1204C>T	LRG_47p1:p.His402Tyr

... more HGVS ... less HGVS

Protein change

H402Y

Other names

p.His402Tyr

Canonical SPDI

NC_000001.11:196690106:C:T

Global minor allele frequency (GMAF) Help The global minor allele frequency calculated by the 1000 Genomes Project. The minor allele at this location is indicated in parentheses and may be different from the allele represented by this VCV record.

0.26657 (C)

Allele frequency Help The frequency of the allele represented by this VCV record.

The Genome Aggregation Database (gnomAD), exomes 0.63577

The Genome Aggregation Database (gnomAD) 0.63625

Trans-Omics for Precision Medicine (TOPMed) 0.66041

1000 Genomes Project 30x 0.72939

1000 Genomes Project 0.73343

The Genome Aggregation Database (gnomAD) 0.64500

Exome Aggregation Consortium (ExAC) 0.67207

The Genome Aggregation Database (gnomAD), exomes 0.67975

Links

ClinGen: CA1305284 dbSNP: rs1061170 VarSome

Genes

Gene	OMIM	ClinGen Gene Dosage Sensitivity Curation		Variation Viewer Help Links to Variation Viewer, a genome browser to view variation data from NCBI databases.	Related variants
Gene	OMIM	HI score Help The haploinsufficiency score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.	TS score Help The triplosensitivity score for the gene, curated by ClinGen’s Dosage Sensitivity Curation task team.		Within gene Help The number of variants in ClinVar that are contained within this gene, with a link to view the list of variants.	All Help The number of variants in ClinVar for this gene, including smaller variants within the gene and larger CNVs that overlap or fully contain the gene.
CFH		-	-	GRCh38 GRCh38 GRCh37	1589	1623

Conditions - Germline

Condition Help The condition for this variant-condition (RCV) record in ClinVar.	Classification Help The aggregate germline classification for this variant-condition (RCV) record in ClinVar. The number of submissions that contribute to this aggregate classification is shown in parentheses. (# of submissions)	Review status Help The aggregate review status for this variant-condition (RCV) record in ClinVar. This value is calculated by NCBI based on data from submitters. Read our rules for calculating the review status.	Last evaluated Help The most recent date that a submitter evaluated this variant for the condition.	Variation/condition record Help The RCV accession number, with most recent version number, for the variant-condition record, with a link to the RCV web page.
Basal laminar drusen	Benign (2)	criteria provided, multiple submitters, no conflicts	Jul 22, 2021	RCV000296616.9
Age related macular degeneration 4	Benign (2)	criteria provided, multiple submitters, no conflicts	Jul 22, 2021	RCV000327040.9
CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II	Benign (1)	criteria provided, single submitter	Apr 27, 2017	RCV000349294.6
Hemolytic uremic syndrome, atypical, susceptibility to, 1	Benign (2)	criteria provided, multiple submitters, no conflicts	Jul 22, 2021	RCV000388493.9
Factor H deficiency	Benign (1)	criteria provided, single submitter	Jul 22, 2021	RCV001579193.4
not provided	Conflicting classifications of pathogenicity (4)	criteria provided, conflicting classifications	Feb 4, 2026	RCV001521610.40
Atypical hemolytic-uremic syndrome	Benign (1)	criteria provided, single submitter	Oct 5, 2022	RCV002294225.3
not specified	Benign (2)	criteria provided, multiple submitters, no conflicts	Jan 21, 2026	RCV006439973.2
Age related macular degeneration 4 Atypical hemolytic-uremic syndrome Basal laminar drusen Factor H deficiency	Benign (1)	criteria provided, single submitter	Oct 2, 2025	RCV005869236.1

Submissions - Germline

Classification Help The submitted germline classification for each SCV record. (Last evaluated)	Review status Help Stars represent the review status, or the level of review supporting the submitted (SCV) record. This value is calculated by NCBI based on data from the submitter. Read our rules for calculating the review status. This column also includes a link to the submitter’s assertion criteria if provided, and the collection method. (Assertion criteria)	Condition Help The condition for the classification, provided by the submitter for this submitted (SCV) record. This column also includes the affected status and allele origin of individuals observed with this variant.	Submitter Help The submitting organization for this submitted (SCV) record. This column also includes the SCV accession and version number, the date this SCV first appeared in ClinVar, and the date that this SCV was last updated in ClinVar.	Expand all rows Collapse all rows Help This column includes more information supporting the classification, including citations, the comment on classification, and detailed evidence provided as observations of the variant by the submitter.
Benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Hemolytic uremic syndrome, atypical, susceptibility to, 1	Illumina Laboratory Services, Illumina Accession: SCV000352393.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Basal laminar drusen	Illumina Laboratory Services, Illumina Accession: SCV000352394.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Membranoproliferative glomerulonephritis with complement factor h deficiency	Illumina Laboratory Services, Illumina Accession: SCV000352395.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Apr 27, 2017) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Age related macular degeneration 4	Illumina Laboratory Services, Illumina Accession: SCV000352392.3 First in ClinVar: Dec 06, 2016 Last updated: May 31, 2020	Publications: PubMed (3) PubMed: 11978762‚ 15761120‚ 16619239 Comment: show This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign. (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (Mar 09, 2020) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV001852119.1 First in ClinVar: Sep 12, 2021 Last updated: Sep 12, 2021	Comment: show This variant is associated with the following publications: (PMID: 26895476, 23497844, 28173125, 29686068, 26376595, 15761120, 20038862, 22875704, 19823576, 20869121, 20378180, 20132989, 22277662, 22552255, 16936732, 24036949, 20581873, 23112567, 22933840, 22509112, 20664795, 18604638, 19399715, 22456601, 24550392, 20660596, 21784901, 21930971, 17339482, 20688737, 20574013, 20538999, 20042647, 18263814, 22388616, 21649859, 17464302, 19000922, 17869048, 19187590, 22197220, 20708732, 22965593, 21825189, 18163432, 25087612) (less) Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Benign (Oct 05, 2022) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Atypical hemolytic-uremic syndrome	Genome Diagnostics Laboratory, The Hospital for Sick Children Accession: SCV002587571.1 First in ClinVar: Oct 29, 2022 Last updated: Oct 29, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal recessive inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005285384.1 First in ClinVar: Sep 29, 2024 Last updated: Sep 29, 2024	Observation: 1 Collection method: not provided Allele origin: germline Affected status: yes Observation 1 Collection method: not provided Allele origin: germline Affected status: yes

Benign (Jul 22, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Basal laminar drusen	Genome-Nilou Lab Accession: SCV001806638.2 First in ClinVar: Aug 25, 2021 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no Sex: mixed

Benign (Jul 22, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Factor H deficiency	Genome-Nilou Lab Accession: SCV001806639.2 First in ClinVar: Aug 25, 2021 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no Sex: mixed

Benign (Jul 22, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hemolytic uremic syndrome, atypical, susceptibility to, 1	Genome-Nilou Lab Accession: SCV001806640.2 First in ClinVar: Aug 25, 2021 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no Sex: mixed

Benign (Jul 22, 2021) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Age related macular degeneration 4	Genome-Nilou Lab Accession: SCV001806641.2 First in ClinVar: Aug 25, 2021 Last updated: Apr 13, 2025	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: no more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: no Sex: mixed

Benign (Feb 04, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	not provided	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001730980.6 First in ClinVar: Jun 15, 2021 Last updated: Feb 23, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Uncertain significance (Apr 01, 2019) C Contributing to aggregate classification	criteria provided, single submitter (CeGaT Center For Human Genetics Tuebingen Variant Classification Criteria Version 2)	not provided	CeGaT Center for Human Genetics Tuebingen Accession: SCV002562958.27 First in ClinVar: Aug 23, 2022 Last updated: Apr 25, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes Number of individuals with the variant: 1

Benign (Oct 02, 2025) C Contributing to aggregate classification	criteria provided, single submitter (Genomenon Sequence Variant Interpretation Standards - Updated)	Basal laminar drusen Age related macular degeneration 4 Atypical hemolytic-uremic syndrome Factor H deficiency Explanation for multiple conditions: Uncertain. The variant was classified for several related diseases, possibly a spectrum of disease; the variant may be associated with one or more the diseases.	Genomenon, Inc, Genomenon, Inc Accession: SCV006580669.1 First in ClinVar: Oct 25, 2025 Last updated: Oct 25, 2025	Comment: show CFH p.His402Tyr (c.1204C>T) is a missense variant that changes the amino acid at residue 402 from Histidine to Tyrosine. This variant is present at high allele frequency in population databases. In conclusion, we classify CFH p.His402Tyr (c.1204C>T) as a benign variant. (less) Observation: 1 Collection method: curation Allele origin: germline Affected status: no Observation 1 Collection method: curation Allele origin: germline Affected status: no

Benign (Apr 10, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Not specified	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV007312488.1 First in ClinVar: Jan 17, 2026 Last updated: Jan 17, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown more Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Number of individuals with the variant: 2843

Benign (Jan 21, 2026) C Contributing to aggregate classification	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	not specified	Women's Health and Genetics/Laboratory Corporation of America, LabCorp Accession: SCV007341528.1 First in ClinVar: Feb 07, 2026 Last updated: Feb 07, 2026	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.

Comment:

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.

Comment:

This variant is associated with the following publications: (PMID: 26895476, 23497844, 28173125, 29686068, 26376595, 15761120, 20038862, 22875704, 19823576, 20869121, 20378180, 20132989, 22277662, 22552255, 16936732, 24036949, 20581873, 23112567, 22933840, 22509112, 20664795, 18604638, 19399715, 22456601, 24550392, 20660596, 21784901, 21930971, 17339482, 20688737, 20574013, 20538999, 20042647, 18263814, 22388616, 21649859, 17464302, 19000922, 17869048, 19187590, 22197220, 20708732, 22965593, 21825189, 18163432, 25087612)

Comment:

CFH p.His402Tyr (c.1204C>T) is a missense variant that changes the amino acid at residue 402 from Histidine to Tyrosine. This variant is present at high allele frequency in population databases. In conclusion, we classify CFH p.His402Tyr (c.1204C>T) as a benign variant.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Long-range PCR facilitates the identification of PMS2-specific mutations.	Clendenning M	Human mutation	2006	PMID: 16619239
Complement factor H variant increases the risk of age-related macular degeneration.	Haines JL	Science (New York, N.Y.)	2005	PMID: 15761120
VSX1: a gene for posterior polymorphous dystrophy and keratoconus.	Héon E	Human molecular genetics	2002	PMID: 11978762

Text-mined citations for rs1061170 ...

These citations are identified by LitVar using the rs number, so they may include citations for more than one variant at this location. Please review the LitVar results carefully for your variant of interest.

Record last updated Apr 26, 2026