Is BGN p.Cys354= (c.1062C>T) pathogenic?

BGN p.Cys354= (c.1062C>T) is classified Likely benign in BGN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-07-27). Very rare (popmax 0.00174%, afr); Associated with Cardiovascular phenotype.

What condition is associated with BGN p.Cys354= (c.1062C>T)?

BGN p.Cys354= (c.1062C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is BGN p.Cys354= (c.1062C>T) in the general population?

BGN p.Cys354= (c.1062C>T) is very rare (popmax 0.00174%, afr) (gnomAD).

BGN p.Cys354=

c.1062C>T · rs782377238 · VCV1780656

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00174%, afr)

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 -13	GERP -4.1
Overall
CADD	3.94	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00174% African / African-American · 1/57,482 alleles

Filtering AF 0.000105% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.1e-05%

Overall 0.000413% 5/1,210,960 alleles · very rare exomes 3/1,097,949 · genomes 2/113,011 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00174%	57,482
European (non-Finnish)	0.000447%	223,866

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.Cys354=
Coding: c.1062C>T
MANE Select: NM_001711
dbSNP: rs782377238
Type: single nucleotide variant
Location: chrX:153508400 (GRCh38)
Structure: AlphaFold pLDDT 85.72
Residue 354: a disulfide bond

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-cys354 (accessed [today's date]).

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