Is BCAP31 p.Phe26Leu (c.78C>A) pathogenic?

BCAP31 p.Phe26Leu (c.78C>A) is classified Uncertain significance in BCAP31 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely pathogenic (0.892); Very rare (popmax 0.000112%, nfe).

How common is BCAP31 p.Phe26Leu (c.78C>A) in the general population?

BCAP31 p.Phe26Leu (c.78C>A) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about BCAP31 p.Phe26Leu (c.78C>A)?

AlphaMissense predicts likely pathogenic (score 0.892) — an in-silico prediction, not a clinical call.

BCAP31 p.Phe26Leu

c.78C>A · rs782161526 · VCV2093059

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.892 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.892	likely pathogenic
REVEL	0.413	indeterminate
SaProt	LLR -6.54	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.22	loss · gain 0.03 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 5.8	GERP -1.9, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 22 kb · p 6.9e-07 · regional, not allelic
Overall
CADD	26.8	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 0.000112% European (non-Finnish) · 1/895,287 alleles

Overall 8.26e-05% 1/1,210,889 alleles · very rare exomes 1/1,097,772 · genomes 0/113,117 · joint denominator

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.Phe26Leu
Coding: c.78C>A
MANE Select: NM_001256447
dbSNP: rs782161526
Type: single nucleotide variant
Location: chrX:153723167 (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.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
BCAP31 p.Lys30Arg 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-phe26leu (accessed [today's date]).

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