Is BGN p.Val74= (c.222T>C) pathogenic?

BGN p.Val74= (c.222T>C) is classified Likely benign in BGN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-09). Very rare (popmax 0.000112%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with BGN p.Val74= (c.222T>C)?

BGN p.Val74= (c.222T>C) is associated with Cardiovascular phenotype (ClinVar).

How common is BGN p.Val74= (c.222T>C) in the general population?

BGN p.Val74= (c.222T>C) is very rare (popmax 0.000112%, nfe) (gnomAD).

BGN p.Val74=

c.222T>C · rs1399581114 · VCV737460

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	donor loss · deltas
Constraint at this position
Conservation	phyloP -0.87	GERP -0.54, phastCons 0.011
Overall
CADD	3.768	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000112% European (non-Finnish) · 1/893,955 alleles

Overall 8.29e-05% 1/1,206,305 alleles · very rare exomes 1/1,092,395 · genomes 0/113,910 · 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.Val74=
Coding: c.222T>C
MANE Select: NM_001711
dbSNP: rs1399581114
Type: single nucleotide variant
Location: chrX:153504853 (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-val74 (accessed [today's date]).

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