Is BCAS1 p.Ala490Val (c.1469C>T) pathogenic?

BCAS1 p.Ala490Val (c.1469C>T) is classified Uncertain significance in BCAS1 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-11-25). AlphaMissense: likely benign (0.158); Ultra-rare (popmax 0.0165%, nfe).

How common is BCAS1 p.Ala490Val (c.1469C>T) in the general population?

BCAS1 p.Ala490Val (c.1469C>T) is ultra-rare (popmax 0.0165%, nfe) (gnomAD).

What do computational predictors say about BCAS1 p.Ala490Val (c.1469C>T)?

AlphaMissense predicts likely benign (score 0.158) — an in-silico prediction, not a clinical call.

BCAS1 p.Ala490Val

c.1469C>T · rs753600225 · VCV2403910

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.158 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.158	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -7.94	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 0.35, phastCons 0.04
Regional constraint	o/e 1.03	unconstrained · MANE · 114 kb · p 0.43 · regional, not allelic
Overall
CADD	19.61	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A445V vs ClinVar A490V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% European (non-Finnish) · 195/1,178,336 alleles

Filtering AF 0.0146% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0139%

Overall 0.0127% 205/1,608,194 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0165%	6,043
Remaining individualsnot grpmax-eligible	0.00803%	12,449
Ashkenazi Jewishnot grpmax-eligible	0.0034%	29,394
Finnishnot grpmax-eligible	0.00313%	31,979
Admixed American	0.00171%	58,454
African / African-American	0.00135%	74,346

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: BCAS1
Protein: p.Ala490Val
Coding: c.1469C>T
MANE Select: NM_001366298
dbSNP: rs753600225
Type: single nucleotide variant
Location: chr20:53966922 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.00
Residue 490: the 'disordered' region

Full BCAS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCAS1 c.1486-10G>A Benign ★★ same type
BCAS1 p.Ala180= Benign ★★ same type
BCAS1 p.Ser519= Benign ★★ same type
BCAS1 p.Thr171Met Benign ★★ ⚠ same type
BCAS1 p.Thr56Met Benign ★★ ⚠ same type
BCAS1 p.Thr578= Benign ★★ same type
BCAS1 p.Thr67Met Benign/Likely benign ★★ ⚠ same type
BCAS1 p.Ala184Val 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/bcas1-p-ala490val (accessed [today's date]).

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