Is BSN p.Ala331Thr (c.991G>A) pathogenic?

BSN p.Ala331Thr (c.991G>A) is classified Likely benign in BSN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-08). AlphaMissense: likely benign (0.061); Ultra-rare (popmax 0.0195%, nfe).

How common is BSN p.Ala331Thr (c.991G>A) in the general population?

BSN p.Ala331Thr (c.991G>A) is ultra-rare (popmax 0.0195%, nfe) (gnomAD).

What do computational predictors say about BSN p.Ala331Thr (c.991G>A)?

AlphaMissense predicts likely benign (score 0.061) — an in-silico prediction, not a clinical call.

BSN p.Ala331Thr

c.991G>A · rs137948444 · VCV2210035

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.061 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0195%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.061	likely benign
REVEL	0.015	strongly benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.12	GERP -4.9
Regional constraint	o/e 0.89	unconstrained · MANE · 98 kb · p 3.9e-05 · regional, not allelic
Overall
CADD	2.417	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 0.0195% European (non-Finnish) · 229/1,173,350 alleles

Filtering AF 0.0174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0166%

Overall 0.016% 257/1,602,336 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0195%	5,124
Middle Eastern	0.0167%	6,006
Remaining individualsnot grpmax-eligible	0.0129%	7,732
African / African-American	0.0107%	9,349
Admixed American	0.00679%	14,737
East Asian	0.00671%	14,897
Ashkenazi Jewishnot grpmax-eligible	0.00346%	28,866
South Asian	0.00333%	30,020

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: BSN
Protein: p.Ala331Thr
Coding: c.991G>A
MANE Select: NM_003458
dbSNP: rs137948444
Type: single nucleotide variant
Location: chr3:49642625 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 (gnomAD)
Residue 331: the 'disordered' region

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

Similar variants

BSN p.Ala1623Thr Uncertain significance ★★ ⚠ same type
BSN p.Ala2329Val Uncertain significance ★★ ⚠ same type
BSN p.Ala2475Pro Uncertain significance ★★ ⚠ same type
BSN p.Arg1145Trp Uncertain significance ★★ ⚠ same type
BSN p.Arg2221His Uncertain significance ★★ ⚠ same type
BSN p.Arg3229Gln Uncertain significance ★★ same type
BSN p.Arg976His Uncertain significance ★★ same type
BSN p.His1842Arg 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/bsn-p-ala331thr (accessed [today's date]).

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