Is BGN p.Val342Ala (c.1025T>C) pathogenic?

BGN p.Val342Ala (c.1025T>C) is classified Uncertain significance in BGN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-27). AlphaMissense: likely pathogenic (0.9449); Very rare (popmax 0.00172%, afr); Associated with Cardiovascular phenotype.

What condition is associated with BGN p.Val342Ala (c.1025T>C)?

BGN p.Val342Ala (c.1025T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is BGN p.Val342Ala (c.1025T>C) in the general population?

BGN p.Val342Ala (c.1025T>C) is very rare (popmax 0.00172%, afr) (gnomAD).

What do computational predictors say about BGN p.Val342Ala (c.1025T>C)?

AlphaMissense predicts likely pathogenic (score 0.9449) — an in-silico prediction, not a clinical call.

BGN p.Val342Ala

c.1025T>C · rs2089818671 · VCV2626585

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9449 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00172%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9449	likely pathogenic
REVEL	0.299	indeterminate
SaProt	LLR -11.59	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,810 bp · p 0.25 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00172% African / African-American · 1/57,973 alleles

Overall 8.25e-05% 1/1,212,171 alleles · very rare exomes 1/1,098,051 · genomes 0/114,120 · joint denominator

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: BGN
Protein: p.Val342Ala
Coding: c.1025T>C
MANE Select: NM_001711
dbSNP: rs2089818671
Type: single nucleotide variant
Location: chrX:153508363 (GRCh38)
Structure: AlphaFold pLDDT 85.72

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

BGN p.Val342Met Uncertain significance ★★ ⚠ same residue
BGN p.Val342= Likely benign ★ same residue
BGN p.Val342Gly Uncertain significance ★ ⚠ same residue
BGN c.909+4A>G Uncertain significance ★★ same condition
BGN p.Ala330Asp Uncertain significance ★★ ⚠ same condition
BGN p.Ala330Pro Uncertain significance ★★ ⚠ same condition
BGN p.Ala41Ser Uncertain significance ★★ ⚠ same condition
BGN p.Ala44Thr Uncertain significance ★★ ⚠ 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/bgn-p-val342ala (accessed [today's date]).

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