Is KIT p.Asn958Ser (c.2873A>G) pathogenic?

KIT p.Asn958Ser (c.2873A>G) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-11-17). AlphaMissense: likely benign (0.1101); Very rare (popmax 0.00669%, eas); Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Asn958Ser (c.2873A>G)?

KIT p.Asn958Ser (c.2873A>G) is associated with hereditary neoplastic syndrome, ovarian cancer, gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Asn958Ser (c.2873A>G) in the general population?

KIT p.Asn958Ser (c.2873A>G) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about KIT p.Asn958Ser (c.2873A>G)?

AlphaMissense predicts likely benign (score 0.1101) — an in-silico prediction, not a clinical call.

KIT p.Asn958Ser

c.2873A>G · rs1060502563 · VCV409772

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1101 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1101	likely benign
REVEL	0.331	indeterminate
SaProt	LLR -5.71	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,746 bp · p 0.88 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00669% East Asian · 3/44,866 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000891%

Overall 0.000929% 15/1,613,984 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,955
Remaining individualsnot grpmax-eligible	0.0048%	20,828
African / African-American	0.00267%	37,457
European (non-Finnish)	0.000593%	168,573

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: KIT
Protein: p.Asn958Ser
Coding: c.2873A>G
MANE Select: NM_000222
dbSNP: rs1060502563
Type: single nucleotide variant
Location: chr4:54738499 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB

Full KIT gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: ovarian cancer gastrointestinal stromal tumor

Similar variants

KIT p.Asn958Asp Uncertain significance ★ ⚠ same residue
KIT p.Asn958Ile Uncertain significance ★ ⚠ same residue
KIT p.Ala621Thr Pathogenic/Likely pathogenic ★★ same condition
KIT p.Asp820Tyr Pathogenic ★★ same condition
KIT p.Gln190Ter Pathogenic ★★ same condition
KIT p.Leu576Pro Pathogenic/Likely pathogenic ★★ same condition
KIT p.Lys642Glu Pathogenic ★★ same condition
KIT p.Trp557Arg Pathogenic/Likely pathogenic ★★ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/kit-p-asn958ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown