Is BGN p.Pro224Arg (c.671C>G) pathogenic?

BGN p.Pro224Arg (c.671C>G) is classified Uncertain significance in BGN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-25). AlphaMissense: likely pathogenic (0.9968); Absent from gnomAD v4.1; Associated with Cardiovascular phenotype.

What condition is associated with BGN p.Pro224Arg (c.671C>G)?

BGN p.Pro224Arg (c.671C>G) is associated with Cardiovascular phenotype (ClinVar).

How common is BGN p.Pro224Arg (c.671C>G) in the general population?

BGN p.Pro224Arg (c.671C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about BGN p.Pro224Arg (c.671C>G)?

AlphaMissense predicts likely pathogenic (score 0.9968) — an in-silico prediction, not a clinical call.

BGN p.Pro224Arg

c.671C>G · VCV3260838

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9968 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.9968	likely pathogenic
REVEL	0.607	indeterminate
SaProt	LLR -13.82	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,810 bp · p 0.25 · regional, not allelic
Overall
CADD	26.6	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

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.Pro224Arg
Coding: c.671C>G
MANE Select: NM_001711
Type: single nucleotide variant
Location: chrX:153506634 (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 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
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-pro224arg (accessed [today's date]).

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