Is BCAP31 p.Arg98Cys (c.292C>T) pathogenic?

BCAP31 p.Arg98Cys (c.292C>T) is classified Uncertain significance in BCAP31 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-02). AlphaMissense: likely pathogenic (0.9694); Very rare (popmax 0.000335%, nfe).

How common is BCAP31 p.Arg98Cys (c.292C>T) in the general population?

BCAP31 p.Arg98Cys (c.292C>T) is very rare (popmax 0.000335%, nfe) (gnomAD).

What do computational predictors say about BCAP31 p.Arg98Cys (c.292C>T)?

AlphaMissense predicts likely pathogenic (score 0.9694) — an in-silico prediction, not a clinical call.

BCAP31 p.Arg98Cys

c.292C>T · rs2091621351 · VCV1375176

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9694 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000335%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9694	likely pathogenic · top 7% in BCAP31
REVEL	0.476	indeterminate
SaProt	LLR -15.75	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 9.6	GERP 1.6, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 22 kb · p 6.9e-07 · regional, not allelic
Overall
CADD	31.0	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 0.000335% European (non-Finnish) · 3/895,277 alleles

Filtering AF 8.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000273% 3/1,097,955 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: BCAP31
Protein: p.Arg98Cys
Coding: c.292C>T
MANE Select: NM_001256447
dbSNP: rs2091621351
Type: single nucleotide variant
Location: chrX:153715591 (GRCh38)
Structure: AlphaFold pLDDT 84.74 · 3 PDB

Full BCAP31 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCAP31 p.Arg98His Uncertain significance ★ ⚠ same residue
BCAP31 p.Arg118Cys Uncertain significance ★★ ⚠ same type
BCAP31 p.Glu245Lys Uncertain significance ★★ ⚠ same type
BCAP31 p.Gly165Arg Uncertain significance ★★ ⚠ same type
BCAP31 p.Gly239Asp Uncertain significance ★★ ⚠ same type
BCAP31 p.Ile56Val Uncertain significance ★★ ⚠ same type
BCAP31 p.Leu226Val Uncertain significance ★★ ⚠ same type
BCAP31 p.Leu40Pro 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/bcap31-p-arg98cys (accessed [today's date]).

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