Is KEAP1 p.Ala30= (c.90G>A) pathogenic?

KEAP1 p.Ala30= (c.90G>A) is classified Benign/Likely benign in KEAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-02-01). Low-frequency (popmax 2.43%, mid).

How common is KEAP1 p.Ala30= (c.90G>A) in the general population?

KEAP1 p.Ala30= (c.90G>A) is low-frequency (popmax 2.43%, mid) (gnomAD).

KEAP1 p.Ala30=

c.90G>A · rs80113737 · VCV720212

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.43%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.038	GERP -4.5, phastCons 0.75
Overall
CADD	7.847	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.43% Middle Eastern · 147/6,042 alleles

Filtering AF 2.11% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.99%

Overall 0.662% 10,646/1,609,122 alleles · low-frequency

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.74%	36
Middle Easterngrpmax	2.43%	41
Finnishnot grpmax-eligible	1.35%	74
Ashkenazi Jewishnot grpmax-eligible	0.871%	115
South Asian	0.856%	117
Remaining individualsnot grpmax-eligible	0.669%	150
European (non-Finnish)	0.666%	150
Admixed American	0.349%	286
African / African-American	0.149%	669
East Asian	0.0335%	2,984

Amish 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.Ala30=
Coding: c.90G>A
MANE Select: NM_203500
dbSNP: rs80113737
Type: single nucleotide variant
Location: chr19:10499944 (GRCh38)
Gene constraint: LOEUF 0.595 · pLI 0.09 (gnomAD)
Structure: AlphaFold pLDDT 90.44 · 122 PDB

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

Similar variants

KEAP1 p.Ala30Val Uncertain significance ★ ⚠ same residue
KEAP1 p.Val31= Benign/Likely benign ★★ 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
KEAP1 p.Arg380Lys 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-ala30 (accessed [today's date]).

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