Is BSG p.Tyr256His (c.766T>C) pathogenic?

BSG p.Tyr256His (c.766T>C) is classified Uncertain significance in BSG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-29). AlphaMissense: likely benign (0.1357); Absent from gnomAD v4.1.

How common is BSG p.Tyr256His (c.766T>C) in the general population?

BSG p.Tyr256His (c.766T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BSG p.Tyr256His (c.766T>C)?

AlphaMissense predicts likely benign (score 0.1357) — an in-silico prediction, not a clinical call.

BSG p.Tyr256His

c.766T>C · rs2512426771 · VCV3135218

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1357 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1357	likely benign
REVEL	0.202	benign-leaning
SaProt	LLR -9.57	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 0.073	GERP -1.5, phastCons 0.14
Regional constraint	o/e 1.08	unconstrained · MANE · 9,939 bp · p 0.057 · regional, not allelic
Overall
CADD	13.24	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: BSG
Protein: p.Tyr256His
Coding: c.766T>C
MANE Select: NM_001728
dbSNP: rs2512426771
Type: single nucleotide variant
Location: chr19:580756 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.51 · 18 PDB
Residue 256: a disulfide bond; a β-strand; the ig-like v-type domain

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

Similar variants

BSG c.*238C>T Benign ★★ same type
BSG p.Ser283= Benign ★★ same type
BSG p.Ala163Thr Uncertain significance ★ ⚠ same type
BSG p.Ala225Pro Uncertain significance ★ ⚠ same type
BSG p.Ala360Thr Uncertain significance ★ ⚠ same type
BSG p.Ala4Gly Uncertain significance ★ ⚠ same type
BSG p.Ala4Thr Uncertain significance ★ ⚠ same type
BSG p.Arg282Gln 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/bsg-p-tyr256his (accessed [today's date]).

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