Is BGN p.Ser253= (c.759C>T) pathogenic?

BGN p.Ser253= (c.759C>T) is classified Likely benign in BGN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-02). Ultra-rare (popmax 0.0148%, eas); Associated with Cardiovascular phenotype.

What condition is associated with BGN p.Ser253= (c.759C>T)?

BGN p.Ser253= (c.759C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is BGN p.Ser253= (c.759C>T) in the general population?

BGN p.Ser253= (c.759C>T) is ultra-rare (popmax 0.0148%, eas) (gnomAD).

BGN p.Ser253=

c.759C>T · rs782302419 · VCV1947070

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0148%, eas)

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 0.23	GERP 0.19, phastCons 0.97
Overall
CADD	8.642	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0148% East Asian · 5/33,759 alleles

Filtering AF 0.00581% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00373%

Overall 0.000661% 8/1,209,876 alleles · ultra-rare exomes 5/1,097,550 · genomes 3/112,326 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0148%	6,752
European (non-Finnish)	0.000335%	298,235

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.Ser253=
Coding: c.759C>T
MANE Select: NM_001711
dbSNP: rs782302419
Type: single nucleotide variant
Location: chrX:153506912 (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-ser253 (accessed [today's date]).

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