Is BSN p.Ala2830Val (c.8489C>T) pathogenic?

BSN p.Ala2830Val (c.8489C>T) is classified Uncertain significance in BSN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0883); Very rare (popmax 0.00831%, nfe).

How common is BSN p.Ala2830Val (c.8489C>T) in the general population?

BSN p.Ala2830Val (c.8489C>T) is very rare (popmax 0.00831%, nfe) (gnomAD).

What do computational predictors say about BSN p.Ala2830Val (c.8489C>T)?

AlphaMissense predicts likely benign (score 0.0883) — an in-silico prediction, not a clinical call.

BSN p.Ala2830Val

c.8489C>T · rs142848835 · VCV2405355

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0883 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00831%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0883	likely benign
REVEL	0.111	moderately 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 4	GERP 2.8, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 12 kb · p 3.9e-13 · regional, not allelic
Overall
CADD	20.6	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 0.00831% European (non-Finnish) · 98/1,179,982 alleles

Filtering AF 0.00697% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.0062% 100/1,613,422 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00831%	12,041
Remaining individualsnot grpmax-eligible	0.0032%	31,240

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.Ala2830Val
Coding: c.8489C>T
MANE Select: NM_003458
dbSNP: rs142848835
Type: single nucleotide variant
Location: chr3:49658045 (GRCh38)
Gene constraint: LOEUF 0.271 · pLI 1.00 (gnomAD)
Residue 2830: the 'interaction with dao' 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-ala2830val (accessed [today's date]).

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