Is BCAS3 p.Met5Val (c.13A>G) pathogenic?

BCAS3 p.Met5Val (c.13A>G) is classified Uncertain significance in BCAS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: likely benign (0.1077); Ultra-rare (popmax 0.0165%, mid).

How common is BCAS3 p.Met5Val (c.13A>G) in the general population?

BCAS3 p.Met5Val (c.13A>G) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about BCAS3 p.Met5Val (c.13A>G)?

AlphaMissense predicts likely benign (score 0.1077) — an in-silico prediction, not a clinical call.

BCAS3 p.Met5Val

c.13A>G · VCV3602136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1077 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1077	likely benign
REVEL	0.307	indeterminate
SaProt	LLR -6.12	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.3, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 689 kb · p 8.1e-12 · regional, not allelic
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0165% Middle Eastern · 1/6,062 alleles

Overall 6.84e-05% 1/1,461,380 alleles · ultra-rare

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: BCAS3
Protein: p.Met5Val
Coding: c.13A>G
MANE Select: NM_017679
Type: single nucleotide variant
Location: chr17:60679470 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.25

Full BCAS3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCAS3 p.Ala349Val Uncertain significance ★★ ⚠ same type
BCAS3 p.Arg254Cys Uncertain significance ★★ ⚠ same type
BCAS3 p.Asp337Glu Uncertain significance ★★ ⚠ same type
BCAS3 p.Pro755Leu Uncertain significance ★★ ⚠ same type
BCAS3 c.1638-10A>G Likely benign ★★ same type
BCAS3 p.Gly159= Likely benign ★★ same type
BCAS3 c.1762+1G>A Likely pathogenic ★ same type
BCAS3 p.Arg544Ter Likely pathogenic ★ 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/bcas3-p-met5val (accessed [today's date]).

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