Is BCAP31 p.Leu40Pro (c.119T>C) pathogenic?

BCAP31 p.Leu40Pro (c.119T>C) is classified Uncertain significance in BCAP31 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-06). AlphaMissense: ambiguous (0.4168); Absent from gnomAD v4.1; Associated with Global developmental delay.

What condition is associated with BCAP31 p.Leu40Pro (c.119T>C)?

BCAP31 p.Leu40Pro (c.119T>C) is associated with Global developmental delay (ClinVar).

How common is BCAP31 p.Leu40Pro (c.119T>C) in the general population?

BCAP31 p.Leu40Pro (c.119T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCAP31 p.Leu40Pro (c.119T>C)?

AlphaMissense predicts ambiguous (score 0.4168) — an in-silico prediction, not a clinical call.

BCAP31 p.Leu40Pro

c.119T>C · rs1057518852 · VCV374039

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4168 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Global developmental delay

Computational evidence

Protein change
AlphaMissense	0.4168	ambiguous
REVEL	0.786	moderately pathogenic-leaning
SaProt	LLR -4.53	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 22 kb · p 6.9e-07 · regional, not allelic
Overall
CADD	26.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BCAP31
Protein: p.Leu40Pro
Coding: c.119T>C
MANE Select: NM_001256447
dbSNP: rs1057518852
Type: single nucleotide variant
Location: chrX:153720946 (GRCh38)
Structure: AlphaFold pLDDT 84.74 · 3 PDB

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

Disease context

Global developmental delay — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BCAP31 p.Leu40Met Uncertain significance ★ ⚠ same residue
BCAP31 p.Leu40= Likely benign ★ 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-leu40pro (accessed [today's date]).

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