Is KIT p.Ile808Phe (c.2422A>T) pathogenic?

KIT p.Ile808Phe (c.2422A>T) is classified Likely pathogenic in KIT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-25). AlphaMissense: likely pathogenic (0.9975); Absent from gnomAD v4.1.

How common is KIT p.Ile808Phe (c.2422A>T) in the general population?

KIT p.Ile808Phe (c.2422A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about KIT p.Ile808Phe (c.2422A>T)?

AlphaMissense predicts likely pathogenic (score 0.9975) — an in-silico prediction, not a clinical call.

KIT p.Ile808Phe

c.2422A>T · rs2475571790 · VCV2579851

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9975 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9975	likely pathogenic ✓ concordant with ClinVar · top 7% in KIT
REVEL	0.948	strongly pathogenic-leaning
SaProt	LLR -14.92	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	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	28.6	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

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.Ile808Phe
Coding: c.2422A>T
MANE Select: NM_000222
dbSNP: rs2475571790
Type: single nucleotide variant
Location: chr4:54733130 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 78.52 · 65 PDB
Residue 808: the protein kinase domain; a β-strand

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

Similar variants

KIT p.Ile808Met Pathogenic ★ same residue
KIT p.Ile808= 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

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-ile808phe (accessed [today's date]).

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