Is BGN p.Ile126= (c.378C>A) pathogenic?

BGN p.Ile126= (c.378C>A) is classified Likely benign in BGN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-29). Ultra-rare (popmax 0.0153%, amr); Associated with Cardiovascular phenotype.

What condition is associated with BGN p.Ile126= (c.378C>A)?

BGN p.Ile126= (c.378C>A) is associated with Cardiovascular phenotype (ClinVar).

How common is BGN p.Ile126= (c.378C>A) in the general population?

BGN p.Ile126= (c.378C>A) is ultra-rare (popmax 0.0153%, amr) (gnomAD).

BGN p.Ile126=

c.378C>A · rs782584801 · VCV1653172

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0153%, amr)

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 1.8	GERP -1.9, phastCons 1
Overall
CADD	9.586	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0153% Admixed American · 7/45,864 alleles

Filtering AF 0.00712% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00506%

Overall 0.000579% 7/1,209,915 alleles · ultra-rare exomes 6/1,097,698 · genomes 1/112,217 · 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.Ile126=
Coding: c.378C>A
MANE Select: NM_001711
dbSNP: rs782584801
Type: single nucleotide variant
Location: chrX:153505889 (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.Ile126Val 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-ile126 (accessed [today's date]).

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