Is BCAS3 p.Pro909Arg (c.2726C>G) pathogenic?

BCAS3 p.Pro909Arg (c.2726C>G) is classified Uncertain significance in BCAS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-19). AlphaMissense: likely benign (0.3388); Ultra-rare (popmax 0.0183%, amr); Associated with Inborn genetic diseases.

What condition is associated with BCAS3 p.Pro909Arg (c.2726C>G)?

BCAS3 p.Pro909Arg (c.2726C>G) is associated with Inborn genetic diseases (ClinVar).

How common is BCAS3 p.Pro909Arg (c.2726C>G) in the general population?

BCAS3 p.Pro909Arg (c.2726C>G) is ultra-rare (popmax 0.0183%, amr) (gnomAD).

What do computational predictors say about BCAS3 p.Pro909Arg (c.2726C>G)?

AlphaMissense predicts likely benign (score 0.3388) — an in-silico prediction, not a clinical call.

BCAS3 p.Pro909Arg

c.2726C>G · rs200061290 · VCV2343285

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3388 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0183%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3388	likely benign
REVEL	0.359	indeterminate
SaProt	LLR -7.23	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 7.7	GERP 2.2, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 24 kb · p 0.21 · regional, not allelic
Overall
CADD	27.5	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 P924R vs ClinVar P909R) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0183% Admixed American · 11/59,970 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00786%

Overall 0.00242% 39/1,613,318 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0183%	5,452
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,861
Remaining individualsnot grpmax-eligible	0.0048%	20,821
European (non-Finnish)	0.00178%	56,185
South Asian	0.0011%	91,040

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.Pro909Arg
Coding: c.2726C>G
MANE Select: NM_017679
dbSNP: rs200061290
Type: single nucleotide variant
Location: chr17:61392109 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.25
Residue 909: a UniProt-annotated variant site (in hemars); the 'disordered' region

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.Ala349Val Uncertain significance ★★ ⚠ same condition
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
BCAS3 p.Ala125Val 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-pro909arg (accessed [today's date]).

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