Is BCAS2 p.His159Gln (c.477T>G) pathogenic?

BCAS2 p.His159Gln (c.477T>G) is classified Uncertain significance in BCAS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-16). AlphaMissense: likely benign (0.0653); Ultra-rare (popmax 0.0154%, sas).

How common is BCAS2 p.His159Gln (c.477T>G) in the general population?

BCAS2 p.His159Gln (c.477T>G) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

What do computational predictors say about BCAS2 p.His159Gln (c.477T>G)?

AlphaMissense predicts likely benign (score 0.0653) — an in-silico prediction, not a clinical call.

BCAS2 p.His159Gln

c.477T>G · rs758805171 · VCV2604051

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0653 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0653	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -3.53	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 0.46	GERP -0.93, phastCons 0.76
Regional constraint	o/e 0.82	unconstrained · MANE · 13 kb · p 0.004 · regional, not allelic
Overall
CADD	10.62	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

Grpmax group 0.0154% South Asian · 14/90,676 alleles

Filtering AF 0.00933% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00738%

Overall 0.000871% 14/1,607,698 alleles · ultra-rare

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: BCAS2
Protein: p.His159Gln
Coding: c.477T>G
MANE Select: NM_005872
dbSNP: rs758805171
Type: single nucleotide variant
Location: chr1:114570066 (GRCh38)
Gene constraint: LOEUF 1.488 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.36 · 26 PDB
Residue 159: an α-helix

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

Similar variants

BCAS2 p.His159Arg Uncertain significance ★ ⚠ same residue
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.Asn133Ser Uncertain significance ★ ⚠ same type
BCAS2 p.Asn220Asp 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-his159gln (accessed [today's date]).

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