Is BOK p.Met15Val (c.43A>G) pathogenic?

BOK p.Met15Val (c.43A>G) is classified Uncertain significance in BOK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-21). AlphaMissense: ambiguous (0.3857); Ultra-rare (popmax 0.0111%, nfe).

How common is BOK p.Met15Val (c.43A>G) in the general population?

BOK p.Met15Val (c.43A>G) is ultra-rare (popmax 0.0111%, nfe) (gnomAD).

What do computational predictors say about BOK p.Met15Val (c.43A>G)?

AlphaMissense predicts ambiguous (score 0.3857) — an in-silico prediction, not a clinical call.

BOK p.Met15Val

c.43A>G · rs201959873 · VCV3134754

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3857 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3857	ambiguous
REVEL	0.048	moderately benign-leaning
SaProt	LLR -6.50	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 0.55, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 13 kb · p 0.022 · regional, not allelic
Overall
CADD	21.0	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 0.0111% European (non-Finnish) · 126/1,140,200 alleles

Filtering AF 0.00943% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00885%

Overall 0.00865% 131/1,514,952 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0111%	9,049
Remaining individualsnot grpmax-eligible	0.00341%	29,323
Finnishnot grpmax-eligible	0.00214%	46,628
African / African-American	0.00143%	69,734
South Asian	0.00124%	80,962

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: BOK
Protein: p.Met15Val
Coding: c.43A>G
MANE Select: NM_032515
dbSNP: rs201959873
Type: single nucleotide variant
Location: chr2:241559526 (GRCh38)
Gene constraint: LOEUF 1.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.33 · 1 PDB
Residue 15: the 'interactions with itpr1' region

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

Similar variants

BOK p.Ala11Val Uncertain significance ★ ⚠ same type
BOK p.Ala12Gly Uncertain significance ★ ⚠ same type
BOK p.Ala141Thr Uncertain significance ★ ⚠ same type
BOK p.Ala148Thr Uncertain significance ★ ⚠ same type
BOK p.Ala192Val Uncertain significance ★ ⚠ same type
BOK p.Ala41Thr Uncertain significance ★ ⚠ same type
BOK p.Ala56Gly Uncertain significance ★ ⚠ same type
BOK p.Ala57Thr 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/bok-p-met15val (accessed [today's date]).

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