Is BGN p.Leu7= (c.21C>T) pathogenic?

BGN p.Leu7= (c.21C>T) is classified Likely benign in BGN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-23). Ultra-rare (popmax 0.0231%, mid); Associated with Cardiovascular phenotype.

What condition is associated with BGN p.Leu7= (c.21C>T)?

BGN p.Leu7= (c.21C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is BGN p.Leu7= (c.21C>T) in the general population?

BGN p.Leu7= (c.21C>T) is ultra-rare (popmax 0.0231%, mid) (gnomAD).

BGN p.Leu7=

c.21C>T · rs199928539 · VCV1930858

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, mid)

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 -3.3	GERP -3.2
Overall
CADD	0.409	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0231% Middle Eastern · 1/4,338 alleles

Filtering AF 0.00868% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0063%

Overall 0.00133% 16/1,206,566 alleles · ultra-rare exomes 13/1,093,731 · genomes 3/112,835 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0231%	4,338
Admixed American	0.0175%	5,726
Remaining individualsnot grpmax-eligible	0.00211%	47,419
African / African-American	0.00174%	57,376
European (non-Finnish)	0.00056%	178,468

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.Leu7=
Coding: c.21C>T
MANE Select: NM_001711
dbSNP: rs199928539
Type: single nucleotide variant
Location: chrX:153504652 (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-leu7 (accessed [today's date]).

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