Is KIT p.Ser365Cys (c.1094C>G) pathogenic?

KIT p.Ser365Cys (c.1094C>G) is classified Uncertain significance in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-04). AlphaMissense: likely benign (0.1354); Absent from gnomAD v4.1.

How common is KIT p.Ser365Cys (c.1094C>G) in the general population?

KIT p.Ser365Cys (c.1094C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KIT p.Ser365Cys (c.1094C>G)?

AlphaMissense predicts likely benign (score 0.1354) — an in-silico prediction, not a clinical call.

KIT p.Ser365Cys

c.1094C>G · rs2109705813 · VCV1684843

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1354 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1354	likely benign
REVEL	0.093	moderately benign-leaning
SaProt	LLR -12.31	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP 0.62, phastCons 0.98
Regional constraint	o/e 0.67	unconstrained · MANE · 32 kb · p 3.4e-16 · regional, not allelic
Overall
CADD	22.0	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

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.Ser365Cys
Coding: c.1094C>G
MANE Select: NM_000222
dbSNP: rs2109705813
Type: single nucleotide variant
Location: chr4:54707266 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 365: the ig-like c2-type 4 domain

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

Similar variants

KIT p.Ser365= Benign/Likely benign ★★ same residue
KIT p.Ala621Thr Pathogenic/Likely pathogenic ★★ same type
KIT p.Asp816His Pathogenic ★★ same type
KIT p.Asp820Tyr Pathogenic ★★ same type
KIT p.Gln190Ter Pathogenic ★★ same type
KIT p.Leu576Pro Pathogenic/Likely pathogenic ★★ same type
KIT p.Lys642Glu Pathogenic ★★ same type
KIT p.Trp557Arg Pathogenic/Likely pathogenic ★★ same type

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-ser365cys (accessed [today's date]).

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