Is KIT p.Cys844Ser (c.2531G>C) pathogenic?

KIT p.Cys844Ser (c.2531G>C) is classified Uncertain significance in KIT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-05). AlphaMissense: likely pathogenic (0.76); Very rare (popmax 0.0011%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Cys844Ser (c.2531G>C)?

KIT p.Cys844Ser (c.2531G>C) is associated with hereditary neoplastic syndrome, gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Cys844Ser (c.2531G>C) in the general population?

KIT p.Cys844Ser (c.2531G>C) is very rare (popmax 0.0011%, nfe) (gnomAD).

What do computational predictors say about KIT p.Cys844Ser (c.2531G>C)?

AlphaMissense predicts likely pathogenic (score 0.76) — an in-silico prediction, not a clinical call.

KIT p.Cys844Ser

c.2531G>C · rs147609111 · VCV409796

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.76 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.76	likely pathogenic
REVEL	0.65	pathogenic-leaning
SaProt	LLR -5.18	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.6, phastCons 1
Regional constraint	o/e 0.46	unconstrained · MANE · 4,810 bp · p 2.2e-10 · regional, not allelic
Overall
CADD	27.5	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 0.0011% European (non-Finnish) · 13/1,179,988 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000867% 14/1,614,134 alleles · very rare exomes 14/1,461,822 · genomes 0/152,312 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0011%	90,768
South Asian	0.0011%	91,088

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.Cys844Ser
Coding: c.2531G>C
MANE Select: NM_000222
dbSNP: rs147609111
Type: single nucleotide variant
Location: chr4:54736544 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 844: the protein kinase 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: gastrointestinal stromal tumor

Similar variants

KIT p.Cys844Arg Uncertain significance ★ ⚠ same residue
KIT p.Cys844Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
KIT p.Cys844= Likely benign ★ 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

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-cys844ser (accessed [today's date]).

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