Is BCAM p.Val358Leu (c.1072G>T) pathogenic?

BCAM p.Val358Leu (c.1072G>T) is classified Uncertain significance in BCAM (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-11). AlphaMissense: likely pathogenic (0.7734); Absent from gnomAD v4.1.

How common is BCAM p.Val358Leu (c.1072G>T) in the general population?

BCAM p.Val358Leu (c.1072G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCAM p.Val358Leu (c.1072G>T)?

AlphaMissense predicts likely pathogenic (score 0.7734) — an in-silico prediction, not a clinical call.

BCAM p.Val358Leu

c.1072G>T · VCV4645337

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7734 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7734	likely pathogenic · top 9% in BCAM
REVEL	0.225	benign-leaning
SaProt	LLR -12.45	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.2	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 12 kb · p 0.64 · regional, not allelic
Overall
CADD	23.6	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: BCAM
Protein: p.Val358Leu
Coding: c.1072G>T
MANE Select: NM_005581
Type: single nucleotide variant
Location: chr19:44814754 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.29 · 2 PDB

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

Similar variants

BCAM p.Arg282His Benign ★★ ⚠ same type
BCAM p.Leu409= Benign ★★ same type
BCAM p.Pro589Leu Likely benign ★★ same type
BCAM p.Thr539Ala Benign ★★ same type
BCAM p.Val381Ile Benign ★★ ⚠ same type
BCAM p.Val540= Benign ★★ same type
BCAM p.Ala129Ser Uncertain significance ★ ⚠ same type
BCAM p.Ala129Thr 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/bcam-p-val358leu (accessed [today's date]).

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