Is KIT p.Ile315Met (c.945C>G) pathogenic?

KIT p.Ile315Met (c.945C>G) is classified Uncertain significance in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-01). AlphaMissense: likely benign (0.1024); Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Ile315Met (c.945C>G)?

KIT p.Ile315Met (c.945C>G) is associated with hereditary neoplastic syndrome (ClinVar).

How common is KIT p.Ile315Met (c.945C>G) in the general population?

KIT p.Ile315Met (c.945C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KIT p.Ile315Met (c.945C>G)?

AlphaMissense predicts likely benign (score 0.1024) — an in-silico prediction, not a clinical call.

KIT p.Ile315Met

c.945C>G · rs2475478307 · VCV1767023

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1024 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.1024	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -8.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 32 kb · p 3.4e-16 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: KIT
Protein: p.Ile315Met
Coding: c.945C>G
MANE Select: NM_000222
dbSNP: rs2475478307
Type: single nucleotide variant
Location: chr4:54707117 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 315: a β-strand

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

Similar variants

KIT p.Ile315Asn Uncertain significance ★★ ⚠ same residue
KIT p.Ile315Thr Uncertain significance ★★ ⚠ same residue
KIT p.Ile315Val Uncertain significance ★★ ⚠ same residue
KIT p.Ile315= Likely benign ★★ same residue
KIT p.Asp820Tyr Pathogenic ★★ same condition
KIT p.Leu576Pro Pathogenic/Likely pathogenic ★★ same condition
KIT p.Trp557Arg Pathogenic/Likely pathogenic ★★ same condition
KIT p.Val559Ala 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-ile315met (accessed [today's date]).

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