Is BOK p.Ser98Tyr (c.293C>A) pathogenic?

BOK p.Ser98Tyr (c.293C>A) is classified Uncertain significance in BOK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-01). AlphaMissense: likely benign (0.2752); Very rare (popmax 0.004%, afr).

How common is BOK p.Ser98Tyr (c.293C>A) in the general population?

BOK p.Ser98Tyr (c.293C>A) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about BOK p.Ser98Tyr (c.293C>A)?

AlphaMissense predicts likely benign (score 0.2752) — an in-silico prediction, not a clinical call.

BOK p.Ser98Tyr

c.293C>A · rs142111641 · VCV2464062

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2752 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2752	likely benign
REVEL	0.349	indeterminate
SaProt	LLR -11.11	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2.4, phastCons 1
Regional constraint	o/e 1.13	unconstrained · MANE · 13 kb · p 0.022 · regional, not allelic
Overall
CADD	24.7	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 0.004% African / African-American · 3/74,942 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,612,318 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.Ser98Tyr
Coding: c.293C>A
MANE Select: NM_032515
dbSNP: rs142111641
Type: single nucleotide variant
Location: chr2:241562420 (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-ser98tyr (accessed [today's date]).

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