Is KIT p.Asp975Asn (c.2923G>A) pathogenic?

KIT p.Asp975Asn (c.2923G>A) is classified Conflicting classifications of pathogenicity in KIT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0961); Ultra-rare (popmax 0.0267%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with KIT p.Asp975Asn (c.2923G>A)?

KIT p.Asp975Asn (c.2923G>A) is associated with hereditary neoplastic syndrome, gastrointestinal stromal tumor (ClinVar).

How common is KIT p.Asp975Asn (c.2923G>A) in the general population?

KIT p.Asp975Asn (c.2923G>A) is ultra-rare (popmax 0.0267%, afr) (gnomAD).

What do computational predictors say about KIT p.Asp975Asn (c.2923G>A)?

AlphaMissense predicts likely benign (score 0.0961) — an in-silico prediction, not a clinical call.

KIT p.Asp975Asn

c.2923G>A · rs373152714 · VCV237272

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0961 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
AlphaMissense	0.0961	likely benign
REVEL	0.39	indeterminate
SaProt	LLR -6.28	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 1,746 bp · p 0.88 · regional, not allelic
Overall
CADD	24.6	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 0.0267% African / African-American · 20/74,890 alleles

Filtering AF 0.0177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0147%

Overall 0.00204% 33/1,613,834 alleles · ultra-rare exomes 19/1,461,736 · genomes 14/152,098 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0267%	3,745
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604
East Asian	0.00223%	44,866
Remaining individualsnot grpmax-eligible	0.0016%	62,484
European (non-Finnish)	0.000847%	117,999

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.Asp975Asn
Coding: c.2923G>A
MANE Select: NM_000222
dbSNP: rs373152714
Type: single nucleotide variant
Location: chr4:54738549 (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

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: gastrointestinal stromal tumor

Similar variants

KIT p.Asp975Glu Uncertain significance ★★ ⚠ same residue
KIT p.Asp975Gly Uncertain significance ★★ ⚠ same residue
KIT p.Asp975His Uncertain significance ★★ ⚠ same residue
KIT p.Asp975Tyr Uncertain significance ★ ⚠ same residue
KIT p.Asp975= Likely benign ★ same residue
KIT p.Asp975del Uncertain significance ★ same residue
KIT p.Asp975fs Uncertain significance ★ same residue
KIT p.Ala621Thr 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-asp975asn (accessed [today's date]).

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