Is BGN p.Leu79= (c.237G>A) pathogenic?

BGN p.Leu79= (c.237G>A) is classified Conflicting classifications of pathogenicity in BGN (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-17). Very rare (popmax 0.00169%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with BGN p.Leu79= (c.237G>A)?

BGN p.Leu79= (c.237G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is BGN p.Leu79= (c.237G>A) in the general population?

BGN p.Leu79= (c.237G>A) is very rare (popmax 0.00169%, nfe) (gnomAD).

BGN p.Leu79=

c.237G>A · rs1164015835 · VCV1380642

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00169%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.35	donor loss · deltas
Constraint at this position
Conservation	phyloP 1.2	GERP 0.77, phastCons 1
Overall
CADD	7.253	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00169% European (non-Finnish) · 15/890,120 alleles

Filtering AF 0.00101% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000802%

Overall 0.00125% 15/1,198,622 alleles · very rare exomes 13/1,086,026 · genomes 2/112,596 · joint denominator

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.Leu79=
Coding: c.237G>A
MANE Select: NM_001711
dbSNP: rs1164015835
Type: single nucleotide variant
Location: chrX:153504868 (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-leu79 (accessed [today's date]).

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