Is KIT p.Val950Met (c.2848G>A) pathogenic?

KIT p.Val950Met (c.2848G>A) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 8 submitters; last evaluated 2026-06-02). AlphaMissense: likely benign (0.0763); Ultra-rare (popmax 0.0329%, mid); Associated with mastocytosis.

What condition is associated with KIT p.Val950Met (c.2848G>A)?

KIT p.Val950Met (c.2848G>A) is associated with mastocytosis, piebaldism, testicular germ cell tumor (ClinVar).

How common is KIT p.Val950Met (c.2848G>A) in the general population?

KIT p.Val950Met (c.2848G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about KIT p.Val950Met (c.2848G>A)?

AlphaMissense predicts likely benign (score 0.0763) — an in-silico prediction, not a clinical call.

KIT p.Val950Met

c.2848G>A · rs146374006 · VCV409716

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.0763 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

mastocytosis

Computational evidence

Protein change
AlphaMissense	0.0763	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -7.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -2.3, phastCons 0.21
Regional constraint	o/e 1.01	unconstrained · MANE · 1,746 bp · p 0.88 · regional, not allelic
Overall
CADD	12.18	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 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00266% 43/1,613,958 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
Admixed American	0.00833%	12,001
South Asian	0.00769%	13,012
Remaining individualsnot grpmax-eligible	0.0048%	20,829
European (non-Finnish)	0.0022%	45,384

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.Val950Met
Coding: c.2848G>A
MANE Select: NM_000222
dbSNP: rs146374006
Type: single nucleotide variant
Location: chr4:54738474 (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

mastocytosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: piebaldism testicular germ cell tumor gastrointestinal stromal tumor hereditary neoplastic syndrome acute myeloid leukemia cutaneous mastocytosis

Similar variants

KIT p.Val950= Likely benign ★★ same residue
KIT p.Val950Leu Uncertain significance ★ ⚠ same residue
KIT p.Ala621Thr Pathogenic/Likely pathogenic ★★ same condition
KIT p.Asp816His 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

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-val950met (accessed [today's date]).

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