Is BCAS3 p.Arg688Pro (c.2063G>C) pathogenic?

BCAS3 p.Arg688Pro (c.2063G>C) is classified Uncertain significance in BCAS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-02). AlphaMissense: likely pathogenic (0.7651); Very rare (popmax 0.00195%, nfe); Associated with Inborn genetic diseases.

What condition is associated with BCAS3 p.Arg688Pro (c.2063G>C)?

BCAS3 p.Arg688Pro (c.2063G>C) is associated with Inborn genetic diseases (ClinVar).

How common is BCAS3 p.Arg688Pro (c.2063G>C) in the general population?

BCAS3 p.Arg688Pro (c.2063G>C) is very rare (popmax 0.00195%, nfe) (gnomAD).

What do computational predictors say about BCAS3 p.Arg688Pro (c.2063G>C)?

AlphaMissense predicts likely pathogenic (score 0.7651) — an in-silico prediction, not a clinical call.

BCAS3 p.Arg688Pro

c.2063G>C · VCV3480034

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7651 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7651	likely pathogenic
REVEL	0.323	indeterminate
SaProt	LLR -5.93	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 689 kb · p 8.1e-12 · regional, not allelic
Overall
CADD	29.3	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 R703P vs ClinVar R688P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00195% European (non-Finnish) · 23/1,179,622 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.00149% 24/1,613,352 alleles · very rare exomes 21/1,461,226 · genomes 3/152,126 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00195%	51,288
Remaining individualsnot grpmax-eligible	0.0016%	62,458

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.Arg688Pro
Coding: c.2063G>C
MANE Select: NM_017679
Type: single nucleotide variant
Location: chr17:61074953 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.25
Residue 703 UniProt numbering: 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.Arg688Ter Likely pathogenic ★ same residue
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

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-arg688pro (accessed [today's date]).

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