Is BOK p.Arg72Cys (c.214C>T) pathogenic?

BOK p.Arg72Cys (c.214C>T) is classified Uncertain significance in BOK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-02). AlphaMissense: likely benign (0.226); Very rare (popmax 0.00414%, amr).

How common is BOK p.Arg72Cys (c.214C>T) in the general population?

BOK p.Arg72Cys (c.214C>T) is very rare (popmax 0.00414%, amr) (gnomAD).

What do computational predictors say about BOK p.Arg72Cys (c.214C>T)?

AlphaMissense predicts likely benign (score 0.226) — an in-silico prediction, not a clinical call.

BOK p.Arg72Cys

c.214C>T · rs1245060908 · VCV2222995

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.226 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00414%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.226	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -10.05	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.9	GERP 0.68, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 13 kb · p 0.022 · regional, not allelic
Overall
CADD	23.9	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 0.00414% Admixed American · 1/24,150 alleles

Overall 0.000657% 1/152,246 alleles · very rare

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.Arg72Cys
Coding: c.214C>T
MANE Select: NM_032515
dbSNP: rs1245060908
Type: single nucleotide variant
Location: chr2:241559697 (GRCh38)
Gene constraint: LOEUF 1.824 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.33 · 1 PDB
Residue 72: an α-helix; the 'nuclear export signal' 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-arg72cys (accessed [today's date]).

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