Is BGN p.Ala330Pro (c.988G>C) pathogenic?

BGN p.Ala330Pro (c.988G>C) is classified Uncertain significance in BGN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-21). AlphaMissense: likely pathogenic (0.64); Ultra-rare (popmax 0.0209%, afr); Associated with Cardiovascular phenotype.

What condition is associated with BGN p.Ala330Pro (c.988G>C)?

BGN p.Ala330Pro (c.988G>C) is associated with Cardiovascular phenotype (ClinVar).

How common is BGN p.Ala330Pro (c.988G>C) in the general population?

BGN p.Ala330Pro (c.988G>C) is ultra-rare (popmax 0.0209%, afr) (gnomAD).

What do computational predictors say about BGN p.Ala330Pro (c.988G>C)?

AlphaMissense predicts likely pathogenic (score 0.64) — an in-silico prediction, not a clinical call.

BGN p.Ala330Pro

c.988G>C · rs1181844672 · VCV1446050

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.64 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0209%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.64	likely pathogenic
REVEL	0.128	moderately benign-leaning
SaProt	LLR -4.10	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,810 bp · p 0.25 · regional, not allelic
Overall
CADD	24.5	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 0.0209% African / African-American · 12/57,464 alleles

Filtering AF 0.012% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00935%

Overall 0.00107% 13/1,210,922 alleles · ultra-rare exomes 7/1,097,976 · genomes 6/112,946 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0209%	4,789
Remaining individualsnot grpmax-eligible	0.0021%	47,620

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.Ala330Pro
Coding: c.988G>C
MANE Select: NM_001711
dbSNP: rs1181844672
Type: single nucleotide variant
Location: chrX:153508326 (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.Ala330Asp Uncertain significance ★★ ⚠ same residue
BGN p.Ala330Val Uncertain significance ★ ⚠ same residue
BGN c.909+4A>G 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
BGN p.Arg170His 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-ala330pro (accessed [today's date]).

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