Is BSG p.Arg349Trp (c.1045C>T) pathogenic?

BSG p.Arg349Trp (c.1045C>T) is classified Uncertain significance in BSG (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-27). AlphaMissense: ambiguous (0.4109); Ultra-rare (popmax 0.0378%, amr).

How common is BSG p.Arg349Trp (c.1045C>T) in the general population?

BSG p.Arg349Trp (c.1045C>T) is ultra-rare (popmax 0.0378%, amr) (gnomAD).

What do computational predictors say about BSG p.Arg349Trp (c.1045C>T)?

AlphaMissense predicts ambiguous (score 0.4109) — an in-silico prediction, not a clinical call.

BSG p.Arg349Trp

c.1045C>T · rs374388470 · VCV2345183

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4109 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0378%, amr)

Computational evidence

Protein change
AlphaMissense	0.4109	ambiguous
REVEL	0.306	indeterminate
SaProt	LLR -13.94	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -3.5, phastCons 0.74
Regional constraint	o/e 1.08	unconstrained · MANE · 9,939 bp · p 0.057 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0378% Admixed American · 22/58,240 alleles

Filtering AF 0.0255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0215%

Overall 0.0189% 302/1,597,920 alleles · ultra-rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.611%	164
Remaining individualsnot grpmax-eligible	0.0421%	2,377
Admixed Americangrpmax	0.0378%	2,647
Middle Eastern	0.0201%	4,986
European (non-Finnish)	0.00588%	17,016
African / African-American	0.00402%	24,859
East Asian	0.00227%	44,124
South Asian	0.00112%	89,112

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg349Trp
Coding: c.1045C>T
MANE Select: NM_001728
dbSNP: rs374388470
Type: single nucleotide variant
Location: chr19:581567 (GRCh38)
Gene constraint: LOEUF 1.254 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.51 · 18 PDB
Residue 349: an α-helix

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-arg349trp (accessed [today's date]).

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