Is BCAS2 p.Asn133Ser (c.398A>G) pathogenic?

BCAS2 p.Asn133Ser (c.398A>G) is classified Uncertain significance in BCAS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-25). AlphaMissense: likely benign (0.0987); Absent from gnomAD v4.1.

How common is BCAS2 p.Asn133Ser (c.398A>G) in the general population?

BCAS2 p.Asn133Ser (c.398A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BCAS2 p.Asn133Ser (c.398A>G)?

AlphaMissense predicts likely benign (score 0.0987) — an in-silico prediction, not a clinical call.

BCAS2 p.Asn133Ser

c.398A>G · rs2526057737 · VCV2286093

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0987 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0987	likely benign
REVEL	0.191	benign-leaning
SaProt	LLR -9.15	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 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 13 kb · p 0.004 · regional, not allelic
Overall
CADD	20.6	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: BCAS2
Protein: p.Asn133Ser
Coding: c.398A>G
MANE Select: NM_005872
dbSNP: rs2526057737
Type: single nucleotide variant
Location: chr1:114575611 (GRCh38)
Gene constraint: LOEUF 1.488 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.36 · 26 PDB
Residue 133: an α-helix

Full BCAS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

BCAS2 p.Ala2Val Uncertain significance ★ ⚠ same type
BCAS2 p.Ala75Val Uncertain significance ★ ⚠ same type
BCAS2 p.Arg222Gln Uncertain significance ★ ⚠ same type
BCAS2 p.Arg76Gln Uncertain significance ★ ⚠ same type
BCAS2 p.Asn123Thr Uncertain significance ★ ⚠ same type
BCAS2 p.Asn220Asp Uncertain significance ★ ⚠ same type
BCAS2 p.Asn48Ser Uncertain significance ★ ⚠ same type
BCAS2 p.Asp20Gly 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/bcas2-p-asn133ser (accessed [today's date]).

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