Is BGN p.Ser42= (c.126G>A) pathogenic?

BGN p.Ser42= (c.126G>A) is classified Likely benign in BGN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-16). Ultra-rare (popmax 0.0457%, mid); Associated with Cardiovascular phenotype.

What condition is associated with BGN p.Ser42= (c.126G>A)?

BGN p.Ser42= (c.126G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is BGN p.Ser42= (c.126G>A) in the general population?

BGN p.Ser42= (c.126G>A) is ultra-rare (popmax 0.0457%, mid) (gnomAD).

BGN p.Ser42=

c.126G>A · rs376287190 · VCV746978

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0457%, mid)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -8.3	GERP -3.5
Overall
CADD	0.049	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0457% Middle Eastern · 2/4,375 alleles

Filtering AF 0.0108% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00829%

Overall 0.00959% 116/1,210,197 alleles · ultra-rare exomes 98/1,097,874 · genomes 18/112,323 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0457%	2,187
African / African-American	0.0192%	5,207
Remaining individualsnot grpmax-eligible	0.0189%	5,288
Admixed American	0.0109%	9,183
European (non-Finnish)	0.00938%	10,658
South Asian	0.00879%	11,371

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.Ser42=
Coding: c.126G>A
MANE Select: NM_001711
dbSNP: rs376287190
Type: single nucleotide variant
Location: chrX:153504757 (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.Ser42Leu 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-ser42 (accessed [today's date]).

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