Is BGN p.Val305Ala (c.914T>C) pathogenic?

BGN p.Val305Ala (c.914T>C) is classified Uncertain significance in BGN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-30). AlphaMissense: likely pathogenic (0.5962); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with BGN p.Val305Ala (c.914T>C)?

BGN p.Val305Ala (c.914T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is BGN p.Val305Ala (c.914T>C) in the general population?

BGN p.Val305Ala (c.914T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BGN p.Val305Ala (c.914T>C)?

AlphaMissense predicts likely pathogenic (score 0.5962) — an in-silico prediction, not a clinical call.

BGN p.Val305Ala

c.914T>C · VCV3480535

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5962 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.5962	likely pathogenic
REVEL	0.216	benign-leaning
SaProt	LLR -10.07	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.1	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,810 bp · p 0.25 · regional, not allelic
Overall
CADD	24.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: BGN
Protein: p.Val305Ala
Coding: c.914T>C
MANE Select: NM_001711
Type: single nucleotide variant
Location: chrX:153508252 (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.Val305Ile 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
BGN p.Arg106His Uncertain significance ★★ ⚠ same condition
BGN p.Arg170Cys 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-val305ala (accessed [today's date]).

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