Is BCAS1 p.Arg609Trp (c.1825C>T) pathogenic?

BCAS1 p.Arg609Trp (c.1825C>T) is classified Uncertain significance in BCAS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: likely benign (0.3211); Ultra-rare (popmax 0.0165%, mid).

How common is BCAS1 p.Arg609Trp (c.1825C>T) in the general population?

BCAS1 p.Arg609Trp (c.1825C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about BCAS1 p.Arg609Trp (c.1825C>T)?

AlphaMissense predicts likely benign (score 0.3211) — an in-silico prediction, not a clinical call.

BCAS1 p.Arg609Trp

c.1825C>T · rs147771144 · VCV2229531

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3211 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3211	likely benign
REVEL	0.369	indeterminate
SaProt	LLR -10.79	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 114 kb · p 0.43 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R564W vs ClinVar R609W) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 0.00215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00191%

Overall 0.0031% 50/1,614,026 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,402
South Asian	0.00549%	18,213
Admixed American	0.00333%	30,000
European (non-Finnish)	0.00297%	33,714
African / African-American	0.00267%	37,514
Remaining individualsnot grpmax-eligible	0.0016%	62,506

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.Arg609Trp
Coding: c.1825C>T
MANE Select: NM_001366298
dbSNP: rs147771144
Type: single nucleotide variant
Location: chr20:53944987 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.00

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-arg609trp (accessed [today's date]).

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