VCV000501335.25 - ClinVar

NM_022489.4(INF2):c.1547C>T (p.Pro516Leu)

Germline

Classification

criteria provided, multiple submitters, no conflicts. Learn more about how ClinVar calculates review status.

Benign/Likely benign
Benign (6); Likely benign (1)

7 out of 8 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_022489.4(INF2):c.1547C>T (p.Pro516Leu)

Variation ID: 501335 Accession: VCV000501335.25

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 14q32.33 14: 104707814 (GRCh38) [ NCBI UCSC ] 14: 105174151 (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	Apr 9, 2018	Sep 22, 2026	Jan 28, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_022489.4:c.1547C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_071934.3:p.Pro516Leu	missense
NM_001031714.4:c.1547C>T	NP_001026884.3:p.Pro516Leu	missense
NC_000014.9:g.104707814C>T
NC_000014.8:g.105174151C>T
NG_027684.1:g.23209C>T

... more HGVS ... less HGVS

Protein change

P516L

Other names

p.Pro516Leu

Canonical SPDI

NC_000014.9:104707813: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.

0.01078 (T)

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

The Genome Aggregation Database (gnomAD), exomes 0.00088

The Genome Aggregation Database (gnomAD), exomes 0.00176

Exome Aggregation Consortium (ExAC) 0.00545

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00671

The Genome Aggregation Database (gnomAD) 0.00721

The Genome Aggregation Database (gnomAD) 0.00779

Trans-Omics for Precision Medicine (TOPMed) 0.00892

1000 Genomes Project 0.01078

1000 Genomes Project 30x 0.01140

Links

ClinGen: CA7372587 dbSNP: rs111589086 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.
INF2		No evidence available	No evidence available	GRCh38 GRCh37	1856	1949

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.
not specified	Benign/Likely benign (4)	criteria provided, multiple submitters, no conflicts	Nov 26, 2024	RCV000591895.8
Charcot-Marie-Tooth disease dominant intermediate E Focal segmental glomerulosclerosis 5	Benign (1)	criteria provided, single submitter	Jan 28, 2026	RCV000861111.11
INF2-related disorder	Benign (1)	no assertion criteria provided	Mar 18, 2019	RCV003915734.2
not provided	Benign (2)	criteria provided, multiple submitters, no conflicts	Oct 1, 2025	RCV004715308.6

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 04, 2017) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification (06012015))	not specified	GeneDx Accession: SCV000714022.1 First in ClinVar: Apr 09, 2018 Last updated: Apr 09, 2018	Comment: show This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. (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 (Apr 07, 2017) C Contributing to aggregate classification	criteria provided, single submitter (EGL Classification Definitions 2015)	not specified	Eurofins Ntd Llc (ga) Accession: SCV000707659.3 First in ClinVar: Apr 02, 2018 Last updated: Apr 13, 2025	Other databases http://www.egl-eurofins.com/emvc… http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=INF2 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: 1 Zygosity: 1 Single Heterozygote Sex: mixed

Benign (Jan 28, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Charcot-Marie-Tooth disease dominant intermediate E Focal segmental glomerulosclerosis 5 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.	Labcorp Genetics (formerly Invitae), Labcorp Accession: SCV001001334.8 First in ClinVar: Dec 17, 2019 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

Benign (-) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	not provided (Autosomal dominant inheritance)	Breakthrough Genomics, Breakthrough Genomics Accession: SCV005294720.1 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 (Jun 14, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Not specified	Mayo Clinic Laboratories, Mayo Clinic Accession: SCV007317844.1 First in ClinVar: Jan 17, 2026 Last updated: Jan 17, 2026	Publications: PubMed (1) PubMed: 35920919 Comment: show BS1, BS2 (less) 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: 14

Benign (Oct 01, 2025) 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: SCV007115562.5 First in ClinVar: Dec 14, 2025 Last updated: Jul 27, 2026	Comment: show INF2: BS1, BS2 (less) 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

Likely benign (Nov 26, 2024) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Not specified	Blueprint Genetics Accession: SCV007797333.1 First in ClinVar: Sep 22, 2026 Last updated: Sep 22, 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

Benign (Mar 18, 2019) N Not contributing to aggregate classification	no assertion criteria provided	INF2-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004731502.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: show This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). (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

Comment:

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

Citations for germline classification of this variant

Title	Author	Journal	Year	Link
Causal and putative pathogenic mutations identified in 39% of children with primary steroid-resistant nephrotic syndrome in South Africa.	Nandlal L	European journal of pediatrics	2022	PMID: 35920919
http://www.egl-eurofins.com/emvclass/emvclass.php?approved_symbol=INF2	-	-	-	-

Text-mined citations for rs111589086 ...

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 Sep 27, 2026