Is BGN p.Glu40= (c.120A>G) pathogenic?

BGN p.Glu40= (c.120A>G) is classified Benign in BGN (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 6.93%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with BGN p.Glu40= (c.120A>G)?

BGN p.Glu40= (c.120A>G) is associated with Cardiovascular phenotype (ClinVar).

BGN p.Glu40=

Q: How common is BGN p.Glu40= (c.120A>G) in the general population?

BGN p.Glu40= (c.120A>G) is common (popmax 6.93%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.120A>G · rs34441665 · VCV716261

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 6.93%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 1.5	GERP -2.3, phastCons 1
Overall
CADD	3.431	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.93% African / African-American · 3,969/57,299 alleles

Filtering AF 6.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.67%

Overall 0.358% 4,338/1,210,181 alleles · common exomes 2,202/1,097,838 · genomes 2,136/112,343 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.93%	14
Remaining individualsnot grpmax-eligible	0.378%	265
Admixed American	0.292%	343
Middle Eastern	0.0689%	1,451
South Asian	0.0123%	8,122
European (non-Finnish)	0.00503%	19,893

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.Glu40=
Coding: c.120A>G
MANE Select: NM_001711
dbSNP: rs34441665
Type: single nucleotide variant
Location: chrX:153504751 (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.Glu40Gln 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-glu40 (accessed [today's date]).

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