Is BCAP31 p.Pro25Ser (c.73C>T) pathogenic?

BCAP31 p.Pro25Ser (c.73C>T) is classified Uncertain significance in BCAP31 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-08). AlphaMissense: likely pathogenic (0.9133); Very rare (popmax 0.00352%, sas).

How common is BCAP31 p.Pro25Ser (c.73C>T) in the general population?

BCAP31 p.Pro25Ser (c.73C>T) is very rare (popmax 0.00352%, sas) (gnomAD).

What do computational predictors say about BCAP31 p.Pro25Ser (c.73C>T)?

AlphaMissense predicts likely pathogenic (score 0.9133) — an in-silico prediction, not a clinical call.

BCAP31 p.Pro25Ser

c.73C>T · rs782786816 · VCV1720689

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9133 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00352%, sas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9133	likely pathogenic
REVEL	0.857	moderately pathogenic-leaning
SaProt	LLR -14.17	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 22 kb · p 6.9e-07 · regional, not allelic
Overall
CADD	28.1	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 0.00352% South Asian · 2/56,870 alleles

Filtering AF 0.000583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000218%

Overall 0.000273% 3/1,097,738 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00352%	28,435
Remaining individualsnot grpmax-eligible	0.0021%	47,625

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.Pro25Ser
Coding: c.73C>T
MANE Select: NM_001256447
dbSNP: rs782786816
Type: single nucleotide variant
Location: chrX:153723172 (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.Pro25= Likely benign ★★ same residue
BCAP31 p.Pro25Thr 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

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-pro25ser (accessed [today's date]).

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