Is KEAP1 p.Val369Ala (c.1106T>C) pathogenic?

KEAP1 p.Val369Ala (c.1106T>C) is classified Likely benign in KEAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-16). AlphaMissense: likely benign (0.1395); Rare (popmax 0.14%, nfe).

How common is KEAP1 p.Val369Ala (c.1106T>C) in the general population?

KEAP1 p.Val369Ala (c.1106T>C) is rare (popmax 0.14%, nfe) (gnomAD).

What do computational predictors say about KEAP1 p.Val369Ala (c.1106T>C)?

AlphaMissense predicts likely benign (score 0.1395) — an in-silico prediction, not a clinical call.

KEAP1 p.Val369Ala

c.1106T>C · rs149721624 · VCV726614

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1395 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.14%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1395	likely benign
REVEL	0.544	indeterminate
SaProt	LLR -8.55	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.1, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 5,271 bp · p 3e-08 · regional, not allelic
Overall
CADD	23.6	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 0.14% European (non-Finnish) · 1,640/1,168,810 alleles

Filtering AF 0.135% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.132%

Overall 0.131% 2,088/1,590,412 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.842%	119
Amishnot grpmax-eligible	0.329%	304
Remaining individualsnot grpmax-eligible	0.187%	535
European (non-Finnish)grpmax	0.14%	713
Middle Eastern	0.1%	1,000
Admixed American	0.0591%	1,693
South Asian	0.0259%	3,863
Finnishnot grpmax-eligible	0.0178%	5,607
African / African-American	0.0161%	6,197

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: KEAP1
Protein: p.Val369Ala
Coding: c.1106T>C
MANE Select: NM_203500
dbSNP: rs149721624
Type: single nucleotide variant
Location: chr19:10491796 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 90.44 · 122 PDB
Residue 369: a β-strand

Full KEAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

KEAP1 p.Ala30= Benign/Likely benign ★★ same type
KEAP1 p.Val31= Benign/Likely benign ★★ same type
KEAP1 p.Ala30Val Uncertain significance ★ ⚠ same type
KEAP1 p.Ala331Val Uncertain significance ★ ⚠ same type
KEAP1 p.Ala376Thr Uncertain significance ★ ⚠ same type
KEAP1 p.Ala407Thr Uncertain significance ★ ⚠ same type
KEAP1 p.Arg15Gln Uncertain significance ★ ⚠ same type
KEAP1 p.Arg326His Uncertain significance ★ ⚠ 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/keap1-p-val369ala (accessed [today's date]).

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