Is BCAS3 p.Ala349Val (c.1046C>T) pathogenic?

BCAS3 p.Ala349Val (c.1046C>T) is classified Uncertain significance in BCAS3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-12-13). AlphaMissense: likely pathogenic (0.9204); Very rare (popmax 0.00398%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BCAS3 p.Ala349Val (c.1046C>T)?

BCAS3 p.Ala349Val (c.1046C>T) is associated with Inborn genetic diseases (ClinVar).

How common is BCAS3 p.Ala349Val (c.1046C>T) in the general population?

BCAS3 p.Ala349Val (c.1046C>T) is very rare (popmax 0.00398%, nfe) (gnomAD).

What do computational predictors say about BCAS3 p.Ala349Val (c.1046C>T)?

AlphaMissense predicts likely pathogenic (score 0.9204) — an in-silico prediction, not a clinical call.

BCAS3 p.Ala349Val

c.1046C>T · rs748056472 · VCV2136284

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9204 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00398%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9204	likely pathogenic
REVEL	0.487	indeterminate
SaProt	LLR -9.52	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.7, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 689 kb · p 8.1e-12 · regional, not allelic
Overall
CADD	28.4	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 0.00398% European (non-Finnish) · 47/1,179,758 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00298% 48/1,612,836 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00398%	25,101
African / African-American	0.00134%	74,652

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.Ala349Val
Coding: c.1046C>T
MANE Select: NM_017679
dbSNP: rs748056472
Type: single nucleotide variant
Location: chr17:60924459 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.25
Residue 349: a UniProt-annotated variant site (in hemars)

Full BCAS3 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

BCAS3 p.Ala349Pro Uncertain significance ★ ⚠ same residue
BCAS3 p.Ala349= Likely benign ★ same residue
BCAS3 p.Arg254Cys Uncertain significance ★★ ⚠ same condition
BCAS3 p.Asp337Glu Uncertain significance ★★ ⚠ same condition
BCAS3 p.Pro755Leu Uncertain significance ★★ ⚠ same condition
BCAS3 p.Gly159= Likely benign ★★ same condition
BCAS3 c.1638-7789T>C Uncertain significance ★ ⚠ same condition
BCAS3 c.661+6T>C 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/bcas3-p-ala349val (accessed [today's date]).

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