VCV000464253.65 - ClinVar

NM_001244008.2(KIF1A):c.4612C>T (p.Arg1538Cys)

Germline

Classification

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

Conflicting classifications of pathogenicity
Uncertain significance(2); Likely benign(3)

5 out of 6 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_001244008.2(KIF1A):c.4612C>T (p.Arg1538Cys)

Variation ID: 464253 Accession: VCV000464253.65

Type and length

single nucleotide variant, 1 bp

Location

Cytogenetic: 2q37.3 2: 240722509 (GRCh38) [ NCBI UCSC ] 2: 241661926 (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	Feb 23, 2026	Feb 3, 2026

HGVS

Nucleotide	Protein	Molecular consequence
NM_001244008.2:c.4612C>T MANE Select Help Transcripts from the Matched Annotation from the NCBI and EMBL-EBI (MANE) collaboration.	NP_001230937.1:p.Arg1538Cys	missense
NM_001244008.1:c.4612C>T
NM_001320705.2:c.4336C>T	NP_001307634.1:p.Arg1446Cys	missense
NM_001330289.2:c.4363C>T	NP_001317218.1:p.Arg1455Cys	missense
NM_001330290.2:c.4411C>T	NP_001317219.1:p.Arg1471Cys	missense
NM_001379631.1:c.4687C>T	NP_001366560.1:p.Arg1563Cys	missense
NM_001379632.1:c.4588C>T	NP_001366561.1:p.Arg1530Cys	missense
NM_001379633.1:c.4585C>T	NP_001366562.1:p.Arg1529Cys	missense
NM_001379634.1:c.4438C>T	NP_001366563.1:p.Arg1480Cys	missense
NM_001379635.1:c.4435C>T	NP_001366564.1:p.Arg1479Cys	missense
NM_001379636.1:c.4423C>T	NP_001366565.1:p.Arg1475Cys	missense
NM_001379637.1:c.4384C>T	NP_001366566.1:p.Arg1462Cys	missense
NM_001379638.1:c.4360C>T	NP_001366567.1:p.Arg1454Cys	missense
NM_001379639.1:c.4333C>T	NP_001366568.1:p.Arg1445Cys	missense
NM_001379640.1:c.4306C>T	NP_001366569.1:p.Arg1436Cys	missense
NM_001379641.1:c.4309C>T	NP_001366570.1:p.Arg1437Cys	missense
NM_001379642.1:c.4612C>T	NP_001366571.1:p.Arg1538Cys	missense
NM_001379645.1:c.4585C>T	NP_001366574.1:p.Arg1529Cys	missense
NM_001379646.1:c.4435C>T	NP_001366575.1:p.Arg1479Cys	missense
NM_001379648.1:c.4411C>T	NP_001366577.1:p.Arg1471Cys	missense
NM_001379649.1:c.4336C>T	NP_001366578.1:p.Arg1446Cys	missense
NM_001379650.1:c.4309C>T	NP_001366579.1:p.Arg1437Cys	missense
NM_001379651.1:c.4309C>T	NP_001366580.1:p.Arg1437Cys	missense
NM_001379653.1:c.4309C>T	NP_001366582.1:p.Arg1437Cys	missense
NM_004321.8:c.4309C>T	NP_004312.2:p.Arg1437Cys	missense
NC_000002.12:g.240722509G>A
NC_000002.11:g.241661926G>A
NG_029724.1:g.102699C>T
LRG_367:g.102699C>T
LRG_367t1:c.4612C>T

... more HGVS ... less HGVS

Protein change

R1437C, R1538C, R1471C, R1446C, R1455C, R1436C, R1445C, R1454C, R1462C, R1475C, R1479C, R1480C, R1529C, R1530C, R1563C

Other names

Canonical SPDI

NC_000002.12:240722508:G:A

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.

0.00140 (A)

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

The Genome Aggregation Database (gnomAD), exomes 0.00021

The Genome Aggregation Database (gnomAD), exomes 0.00055

Exome Aggregation Consortium (ExAC) 0.00132

1000 Genomes Project 0.00140

The Genome Aggregation Database (gnomAD) 0.00141

The Genome Aggregation Database (gnomAD) 0.00150

1000 Genomes Project 30x 0.00156

Trans-Omics for Precision Medicine (TOPMed) 0.00179

NHLBI Exome Sequencing Project (ESP) Exome Variant Server 0.00188

Links

ClinGen: CA2207376 dbSNP: rs200184619 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.
KIF1A		No evidence available	No evidence available	GRCh38 GRCh37	3348	3584

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.
Hereditary spastic paraplegia 30 Intellectual disability, autosomal dominant 9 Neuropathy, hereditary sensory, type 2C	Likely benign (1)	criteria provided, single submitter	Feb 3, 2026	RCV000554693.23
Hereditary spastic paraplegia 30	Uncertain significance (1)	criteria provided, single submitter	Jan 13, 2018	RCV001136789.12
not provided	Likely benign (2)	criteria provided, multiple submitters, no conflicts	Dec 22, 2020	RCV001697024.14
Hereditary spastic paraplegia	Uncertain significance (1)	criteria provided, single submitter	Dec 12, 2016	RCV001848938.11
KIF1A-related disorder	Likely benign (1)	no assertion criteria provided	Apr 28, 2021	RCV004541685.2

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.
Uncertain significance (Jan 13, 2018) C Contributing to aggregate classification	criteria provided, single submitter (ICSL Variant Classification Criteria 13 December 2019)	Spastic paraplegia 30A, autosomal dominant	Illumina Laboratory Services, Illumina Accession: SCV001296659.1 First in ClinVar: May 31, 2020 Last updated: May 31, 2020	Comment: show This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. (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

Likely benign (Nov 23, 2019) C Contributing to aggregate classification	criteria provided, single submitter (ARUP Molecular Germline Variant Investigation Process)	not provided	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories Accession: SCV001474607.1 First in ClinVar: Jan 26, 2021 Last updated: Jan 26, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: unknown Observation 1 Collection method: clinical testing Allele origin: germline Affected status: unknown

Likely benign (Dec 22, 2020) C Contributing to aggregate classification	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	not provided	GeneDx Accession: SCV000725986.2 First in ClinVar: Apr 09, 2018 Last updated: Sep 26, 2021	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Uncertain significance (Dec 12, 2016) C Contributing to aggregate classification	criteria provided, single submitter (ACMG Guidelines, 2015)	Hereditary spastic paraplegia	Genome Diagnostics Laboratory, The Hospital for Sick Children Accession: SCV002105244.1 First in ClinVar: Mar 19, 2022 Last updated: Mar 19, 2022	Observation: 1 Collection method: clinical testing Allele origin: germline Affected status: yes Observation 1 Collection method: clinical testing Allele origin: germline Affected status: yes

Likely benign (Feb 03, 2026) C Contributing to aggregate classification	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Hereditary spastic paraplegia 30 Neuropathy, hereditary sensory, type 2C Intellectual disability, autosomal dominant 9 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: SCV000638618.11 First in ClinVar: Dec 26, 2017 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

Likely benign (Apr 28, 2021) N Not contributing to aggregate classification	no assertion criteria provided	KIF1A-related condition	PreventionGenetics, part of Exact Sciences Accession: SCV004783012.2 First in ClinVar: Mar 16, 2024 Last updated: Oct 08, 2024	Comment: show This variant is classified as likely 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 was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

Citations for germline classification of this variant

There are no citations for germline classification of this variant in ClinVar. If you know of citations for this variation, please consider submitting that information to ClinVar.

Text-mined citations for rs200184619 ...

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 Mar 01, 2026