Is BCAS1 p.Ser135Cys (c.403A>T) pathogenic?

BCAS1 p.Ser135Cys (c.403A>T) is classified Uncertain significance in BCAS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: likely benign (0.2363); Absent from gnomAD v4.1.

How common is BCAS1 p.Ser135Cys (c.403A>T) in the general population?

BCAS1 p.Ser135Cys (c.403A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCAS1 p.Ser135Cys (c.403A>T)?

AlphaMissense predicts likely benign (score 0.2363) — an in-silico prediction, not a clinical call.

BCAS1 p.Ser135Cys

c.403A>T · VCV3823051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2363 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2363	likely benign
REVEL	0.133	moderately benign-leaning
SaProt	LLR -8.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.56 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.1	GERP 1.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 114 kb · p 0.43 · regional, not allelic
Overall
CADD	24.1	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.

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: BCAS1
Protein: p.Ser135Cys
Coding: c.403A>T
MANE Select: NM_001366298
Type: single nucleotide variant
Location: chr20:54028712 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.00
Residue 135: 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-ser135cys (accessed [today's date]).

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