Is BCAP31 p.Pro240Leu (c.719C>T) pathogenic?

BCAP31 p.Pro240Leu (c.719C>T) is classified Conflicting classifications of pathogenicity in BCAP31 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-03-27). AlphaMissense: likely benign (0.1245); Ultra-rare (popmax 0.0207%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BCAP31 p.Pro240Leu (c.719C>T)?

BCAP31 p.Pro240Leu (c.719C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BCAP31 p.Pro240Leu (c.719C>T) in the general population?

BCAP31 p.Pro240Leu (c.719C>T) is ultra-rare (popmax 0.0207%, nfe) (gnomAD).

What do computational predictors say about BCAP31 p.Pro240Leu (c.719C>T)?

AlphaMissense predicts likely benign (score 0.1245) — an in-silico prediction, not a clinical call.

BCAP31 p.Pro240Leu

c.719C>T · rs200212822 · VCV2414267

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1245 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0207%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1245	likely benign
REVEL	0.023	moderately benign-leaning
SaProt	LLR -10.53	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.4	GERP 1.1, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 22 kb · p 6.9e-07 · regional, not allelic
Overall
CADD	20.9	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 0.0207% European (non-Finnish) · 185/893,266 alleles

Filtering AF 0.0183% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0173%

Overall 0.0158% 191/1,205,503 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0207%	4,828
Remaining individualsnot grpmax-eligible	0.00632%	15,811
African / African-American	0.00352%	28,414
Admixed American	0.00221%	45,273

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.Pro240Leu
Coding: c.719C>T
MANE Select: NM_001256447
dbSNP: rs200212822
Type: single nucleotide variant
Location: chrX:153700959 (GRCh38)
Structure: AlphaFold pLDDT 84.74 · 3 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCAP31 p.Pro240Arg Uncertain significance ★ ⚠ same residue
BCAP31 p.Glu245Lys Uncertain significance ★★ ⚠ same condition
BCAP31 p.Gly165Arg Uncertain significance ★★ ⚠ same condition
BCAP31 p.Ile56Val Uncertain significance ★★ ⚠ same condition
BCAP31 p.Leu226Val Uncertain significance ★★ ⚠ same condition
BCAP31 p.Lys30Arg Uncertain significance ★★ ⚠ same condition
BCAP31 p.Ter247Gln Likely pathogenic ★ same condition
BCAP31 c.-44-276A>G Uncertain significance ★ same condition

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-pro240leu (accessed [today's date]).

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