Is BCAS1 p.Ser426Pro (c.1276T>C) pathogenic?

BCAS1 p.Ser426Pro (c.1276T>C) is classified Uncertain significance in BCAS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-27). AlphaMissense: likely benign (0.3396); Rare (popmax 0.12%, afr).

How common is BCAS1 p.Ser426Pro (c.1276T>C) in the general population?

BCAS1 p.Ser426Pro (c.1276T>C) is rare (popmax 0.12%, afr) (gnomAD).

What do computational predictors say about BCAS1 p.Ser426Pro (c.1276T>C)?

AlphaMissense predicts likely benign (score 0.3396) — an in-silico prediction, not a clinical call.

BCAS1 p.Ser426Pro

c.1276T>C · rs199964006 · VCV3133297

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3396 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.12%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3396	likely benign
REVEL	0.176	moderately benign-leaning
SaProt	LLR -7.42	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.26	donor gain · deltas
Constraint at this position
Conservation	phyloP 9.4	GERP 2.2, 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

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 S381P vs ClinVar S426P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.12% African / African-American · 90/74,950 alleles

Filtering AF 0.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0926%

Overall 0.00565% 91/1,611,800 alleles · rare exomes 40/1,459,590 · genomes 51/152,210 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.12%	833
Admixed American	0.00167%	59,922

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.Ser426Pro
Coding: c.1276T>C
MANE Select: NM_001366298
dbSNP: rs199964006
Type: single nucleotide variant
Location: chr20:53975430 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 51.00
Residue 381 UniProt numbering: a modified residue (phosphoserine)

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-ser426pro (accessed [today's date]).

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