Is BOK p.Pro82Leu (c.245C>T) pathogenic?

BOK p.Pro82Leu (c.245C>T) is classified Uncertain significance in BOK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-08). AlphaMissense: likely pathogenic (0.9187); Very rare (popmax 0.00416%, nfe).

How common is BOK p.Pro82Leu (c.245C>T) in the general population?

BOK p.Pro82Leu (c.245C>T) is very rare (popmax 0.00416%, nfe) (gnomAD).

What do computational predictors say about BOK p.Pro82Leu (c.245C>T)?

AlphaMissense predicts likely pathogenic (score 0.9187) — an in-silico prediction, not a clinical call.

BOK p.Pro82Leu

c.245C>T · VCV3992376

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9187 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00416%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9187	likely pathogenic
REVEL	0.381	indeterminate
SaProt	LLR -11.35	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.4, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 13 kb · p 0.022 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00416% European (non-Finnish) · 49/1,178,830 alleles

Filtering AF 0.00318% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00287%

Overall 0.00323% 52/1,609,752 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00416%	24,058
Remaining individualsnot grpmax-eligible	0.00321%	31,181
African / African-American	0.00134%	74,894

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.Pro82Leu
Coding: c.245C>T
MANE Select: NM_032515
Type: single nucleotide variant
Location: chr2:241562372 (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.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-pro82leu (accessed [today's date]).

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