Is BOK p.Val191Leu (c.571G>T) pathogenic?

BOK p.Val191Leu (c.571G>T) is classified Uncertain significance in BOK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-14). AlphaMissense: likely benign (0.1106); Ultra-rare (popmax 0.04%, afr).

How common is BOK p.Val191Leu (c.571G>T) in the general population?

BOK p.Val191Leu (c.571G>T) is ultra-rare (popmax 0.04%, afr) (gnomAD).

What do computational predictors say about BOK p.Val191Leu (c.571G>T)?

AlphaMissense predicts likely benign (score 0.1106) — an in-silico prediction, not a clinical call.

BOK p.Val191Leu

c.571G>T · VCV3481542

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1106 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.04%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1106	likely benign
REVEL	0.043	moderately benign-leaning
SaProt	LLR -6.09	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 6.2	GERP -0.78, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 13 kb · p 0.022 · regional, not allelic
Overall
CADD	13.21	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.04% African / African-American · 30/74,932 alleles

Filtering AF 0.0288% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0249%

Overall 0.00224% 36/1,609,512 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.04%	2,498
Admixed American	0.00334%	29,945
Remaining individualsnot grpmax-eligible	0.0032%	31,209
South Asian	0.0011%	90,842
European (non-Finnish)	8.48e-05%	1,179,711

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.Val191Leu
Coding: c.571G>T
MANE Select: NM_032515
Type: single nucleotide variant
Location: chr2:241572354 (GRCh38)
Gene constraint: LOEUF 1.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.33 · 1 PDB

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

Similar variants

BOK p.Val191Met Uncertain significance ★ ⚠ same residue
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

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-val191leu (accessed [today's date]).

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