Is BSG p.Arg282Gln (c.845G>A) pathogenic?

BSG p.Arg282Gln (c.845G>A) is classified Uncertain significance in BSG (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-23). AlphaMissense: likely benign (0.0903); Ultra-rare (popmax 0.0176%, sas).

How common is BSG p.Arg282Gln (c.845G>A) in the general population?

BSG p.Arg282Gln (c.845G>A) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

What do computational predictors say about BSG p.Arg282Gln (c.845G>A)?

AlphaMissense predicts likely benign (score 0.0903) — an in-silico prediction, not a clinical call.

BSG p.Arg282Gln

c.845G>A · rs776051567 · VCV2550661

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0903 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0903	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -7.22	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 -1.6	GERP -2.6
Regional constraint	o/e 1.08	unconstrained · MANE · 9,939 bp · p 0.057 · regional, not allelic
Overall
CADD	0.408	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 0.0176% South Asian · 16/91,090 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00888%

Overall 0.00149% 24/1,612,686 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,693
Admixed American	0.00167%	60,000
Remaining individualsnot grpmax-eligible	0.0016%	62,466
European (non-Finnish)	0.000508%	196,658

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: BSG
Protein: p.Arg282Gln
Coding: c.845G>A
MANE Select: NM_001728
dbSNP: rs776051567
Type: single nucleotide variant
Location: chr19:581367 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.51 · 18 PDB
Residue 282: 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.Arg300Gln 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-arg282gln (accessed [today's date]).

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