Is BCAS3 p.Ser709Tyr (c.2126C>A) pathogenic?

BCAS3 p.Ser709Tyr (c.2126C>A) is classified Uncertain significance in BCAS3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). AlphaMissense: likely pathogenic (0.9738); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with BCAS3 p.Ser709Tyr (c.2126C>A)?

BCAS3 p.Ser709Tyr (c.2126C>A) is associated with Inborn genetic diseases (ClinVar).

How common is BCAS3 p.Ser709Tyr (c.2126C>A) in the general population?

BCAS3 p.Ser709Tyr (c.2126C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCAS3 p.Ser709Tyr (c.2126C>A)?

AlphaMissense predicts likely pathogenic (score 0.9738) — an in-silico prediction, not a clinical call.

BCAS3 p.Ser709Tyr

c.2126C>A · VCV3480043

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9738 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9738	likely pathogenic
REVEL	0.614	indeterminate
SaProt	LLR -9.16	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 7.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 689 kb · p 8.1e-12 · regional, not allelic
Overall
CADD	27.4	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 S724Y vs ClinVar S709Y) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BCAS3
Protein: p.Ser709Tyr
Coding: c.2126C>A
MANE Select: NM_017679
Type: single nucleotide variant
Location: chr17:61075016 (GRCh38)
Gene constraint: LOEUF 0.58 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.25
Residue 709: 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.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-ser709tyr (accessed [today's date]).

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