Is BSG p.Ala225= (c.675T>C) pathogenic?

BSG p.Ala225= (c.675T>C) is classified Benign in BSG (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-21). Common (popmax 47.9%, eas) — too common for a highly-penetrant pathogenic allele; Associated with BSG-related disorder.

What condition is associated with BSG p.Ala225= (c.675T>C)?

BSG p.Ala225= (c.675T>C) is associated with BSG-related disorder (ClinVar).

BSG p.Ala225=

Q: How common is BSG p.Ala225= (c.675T>C) in the general population?

BSG p.Ala225= (c.675T>C) is common (popmax 47.9%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.675T>C · rs4682 · VCV3059879

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 47.9%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

BSG-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -2.4
Overall
CADD	0.023	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 47.9% East Asian · 21,474/44,834 alleles

Filtering AF 47.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 47.1%

Overall 23.8% 380,317/1,599,520 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	47.9%	2
South Asian	33.6%	3
African / African-American	29.6%	3
Admixed American	29.4%	3
Remaining individualsnot grpmax-eligible	24.4%	4
Ashkenazi Jewishnot grpmax-eligible	22.9%	4
European (non-Finnish)	21.9%	5
Middle Eastern	18.5%	5
Finnishnot grpmax-eligible	14.8%	7
Amishnot grpmax-eligible	8.02%	12

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.Ala225=
Coding: c.675T>C
MANE Select: NM_001728
dbSNP: rs4682
Type: single nucleotide variant
Location: chr19:580665 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.51 · 18 PDB
Residue 225: a β-strand; the ig-like v-type domain

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

Disease context

BSG-related disorder

Similar variants

BSG p.Ala225Pro Uncertain significance ★ ⚠ same residue
BSG p.Arg380Cys Uncertain significance ★ ⚠ same condition
BSG c.1095-9G>A Benign same condition
BSG c.-89C>A Likely benign same condition
BSG p.Ala122= Likely benign same condition
BSG p.Asp148= Likely benign same condition
BSG p.Asp181= Benign same condition
BSG p.Ile342= Likely benign same condition

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-ala225 (accessed [today's date]).

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