Is BGN p.Arg280Trp (c.838C>T) pathogenic?

BGN p.Arg280Trp (c.838C>T) is classified Uncertain significance in BGN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). AlphaMissense: likely pathogenic (0.8865); Ultra-rare (popmax 0.0243%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with BGN p.Arg280Trp (c.838C>T)?

BGN p.Arg280Trp (c.838C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is BGN p.Arg280Trp (c.838C>T) in the general population?

BGN p.Arg280Trp (c.838C>T) is ultra-rare (popmax 0.0243%, nfe) (gnomAD).

What do computational predictors say about BGN p.Arg280Trp (c.838C>T)?

AlphaMissense predicts likely pathogenic (score 0.8865) — an in-silico prediction, not a clinical call.

BGN p.Arg280Trp

c.838C>T · rs370486954 · VCV1444541

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.8865 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0243%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.8865	likely pathogenic
REVEL	0.53	indeterminate
SaProt	LLR -11.01	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.81	GERP -4.1, phastCons 0.88
Regional constraint	o/e 0.94	unconstrained · MANE · 3,810 bp · p 0.25 · regional, not allelic
Overall
CADD	22.5	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 0.0243% European (non-Finnish) · 217/892,918 alleles

Filtering AF 0.0216% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0206%

Overall 0.0187% 226/1,205,676 alleles · ultra-rare exomes 214/1,093,095 · genomes 12/112,581 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0243%	4,115
Remaining individualsnot grpmax-eligible	0.00843%	11,859
Finnishnot grpmax-eligible	0.00433%	23,105
African / African-American	0.00349%	28,656
South Asian	0.00179%	56,020

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.Arg280Trp
Coding: c.838C>T
MANE Select: NM_001711
dbSNP: rs370486954
Type: single nucleotide variant
Location: chrX:153507114 (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.Arg280Gln 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-arg280trp (accessed [today's date]).

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