Is BCAS4 p.Ser135= (c.405A>G) pathogenic?

BCAS4 p.Ser135= (c.405A>G) is classified Likely benign in BCAS4 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-24). AlphaMissense: likely benign (0.0655); Ultra-rare (popmax 0.0312%, eas).

How common is BCAS4 p.Ser135= (c.405A>G) in the general population?

BCAS4 p.Ser135= (c.405A>G) is ultra-rare (popmax 0.0312%, eas) (gnomAD).

What do computational predictors say about BCAS4 p.Ser135= (c.405A>G)?

AlphaMissense predicts likely benign (score 0.0655) — an in-silico prediction, not a clinical call.

BCAS4 p.Ser135=

c.405A>G · rs769681815 · VCV2524278

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0655 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0312%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0655	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -7.67	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.45	GERP -2.7
Overall
CADD	0.485	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0312% East Asian · 14/44,870 alleles

Filtering AF 0.0188% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0151%

Overall 0.00093% 15/1,613,376 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0312%	3,205
Remaining individualsnot grpmax-eligible	0.0016%	62,466

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: BCAS4
Protein: p.Ser135=
Coding: c.405A>G
MANE Select: NM_198799
dbSNP: rs769681815
Type: single nucleotide variant
Location: chr20:50876491 (GRCh38)
Gene constraint: LOEUF 1.081 · pLI 0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.40

Full BCAS4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCAS4 p.Ser130Thr Benign ★★ same type
BCAS4 p.Ser130Tyr Benign/Likely benign ★★ ⚠ same type
BCAS4 p.Thr142Met Likely benign ★★ same type
BCAS4 c.-15C>T Uncertain significance ★ ⚠ same type
BCAS4 c.-6C>T Uncertain significance ★ ⚠ same type
BCAS4 p.Ala118Ser Uncertain significance ★ ⚠ same type
BCAS4 p.Ala126Thr Uncertain significance ★ ⚠ same type
BCAS4 p.Ala29Ser 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/bcas4-p-ser135 (accessed [today's date]).

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