Is BAK1 p.Ala28Val (c.83C>T) pathogenic?

BAK1 p.Ala28Val (c.83C>T) is classified Benign in BAK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-28). AlphaMissense: likely benign (0.0995); Low-frequency (popmax 1.97%, eas).

How common is BAK1 p.Ala28Val (c.83C>T) in the general population?

BAK1 p.Ala28Val (c.83C>T) is low-frequency (popmax 1.97%, eas) (gnomAD).

What do computational predictors say about BAK1 p.Ala28Val (c.83C>T)?

AlphaMissense predicts likely benign (score 0.0995) — an in-silico prediction, not a clinical call.

BAK1 p.Ala28Val

c.83C>T · rs4987115 · VCV707918

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0995 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.97%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0995	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -8.06	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.4	GERP -0.95, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 3,798 bp · p 3.2e-07 · regional, not allelic
Overall
CADD	17.96	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 1.97% East Asian · 882/44,884 alleles

Filtering AF 1.86% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.81%

Overall 0.175% 2,825/1,614,148 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.97%	51
South Asian	1.64%	61
Remaining individualsnot grpmax-eligible	0.291%	343
Ashkenazi Jewishnot grpmax-eligible	0.128%	779
Middle Eastern	0.099%	1,010
Admixed American	0.0467%	2,143
African / African-American	0.0386%	2,588
Finnishnot grpmax-eligible	0.0219%	4,573
European (non-Finnish)	0.0129%	7,763

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: BAK1
Protein: p.Ala28Val
Coding: c.83C>T
MANE Select: NM_001188
dbSNP: rs4987115
Type: single nucleotide variant
Location: chr6:33575916 (GRCh38)
Gene constraint: LOEUF 1.197 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.82 · 55 PDB
Residue 28: a UniProt-annotated variant site (in); an α-helix; the 'disordered' region

Full BAK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BAK1 p.Arg127Pro Uncertain significance ★ ⚠ same type
BAK1 p.Arg169Trp Uncertain significance ★ ⚠ same type
BAK1 p.Arg206Gln Uncertain significance ★ ⚠ same type
BAK1 p.Arg207Thr Uncertain significance ★ ⚠ same type
BAK1 p.Arg36His Uncertain significance ★ ⚠ same type
BAK1 p.Arg76Trp Uncertain significance ★ ⚠ same type
BAK1 p.Asn124Ile Uncertain significance ★ ⚠ same type
BAK1 p.Asn124Ser 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/bak1-p-ala28val (accessed [today's date]).

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