Is KIT p.Met318Val (c.952A>G) pathogenic?

KIT p.Met318Val (c.952A>G) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 9 submitters; last evaluated 2026-05-26). AlphaMissense: likely benign (0.0548); Ultra-rare (popmax 0.0176%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Met318Val (c.952A>G)?

KIT p.Met318Val (c.952A>G) is associated with hereditary neoplastic syndrome, mastocytosis, piebaldism (ClinVar).

How common is KIT p.Met318Val (c.952A>G) in the general population?

KIT p.Met318Val (c.952A>G) is ultra-rare (popmax 0.0176%, nfe) (gnomAD).

What do computational predictors say about KIT p.Met318Val (c.952A>G)?

AlphaMissense predicts likely benign (score 0.0548) — an in-silico prediction, not a clinical call.

KIT p.Met318Val

c.952A>G · rs143388949 · VCV161260

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 9 submitters

AlphaMissense

likely benign

0.0548 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0548	likely benign
REVEL	0.295	indeterminate
SaProt	LLR -6.36	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.59 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.87	GERP -4.9, phastCons 0.01
Regional constraint	o/e 0.67	unconstrained · MANE · 32 kb · p 3.4e-16 · regional, not allelic
Overall
CADD	1.3	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 0.0176% European (non-Finnish) · 199/1,131,176 alleles

Filtering AF 0.0156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0148%

Overall 0.0162% 253/1,559,830 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.13%	769
Remaining individualsnot grpmax-eligible	0.0181%	5,511
European (non-Finnish)grpmax	0.0176%	5,684
Finnishnot grpmax-eligible	0.00313%	31,997
African / African-American	0.00271%	36,854
Admixed American	0.00167%	59,842

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Met318Val
Coding: c.952A>G
MANE Select: NM_000222
dbSNP: rs143388949
Type: single nucleotide variant
Location: chr4:54707124 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 318: a β-strand; the ig-like c2-type 4 domain

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: mastocytosis piebaldism gastrointestinal stromal tumor

Similar variants

KIT p.Met318Ile Uncertain significance ★★ ⚠ same residue
KIT p.Met318Leu Uncertain significance ★★ ⚠ same residue
KIT p.Met318Lys Uncertain significance ★ ⚠ same residue
KIT p.Met318Thr Uncertain significance ★ ⚠ same residue
KIT p.Met318fs Likely benign ★ same residue
KIT p.Ala621Thr Pathogenic/Likely pathogenic ★★ same condition
KIT p.Asp820Tyr Pathogenic ★★ same condition
KIT p.Gln190Ter 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-met318val (accessed [today's date]).

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