Is BGN p.Ser180= (c.540C>T) pathogenic?

BGN p.Ser180= (c.540C>T) is classified Benign in BGN (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-02-04). Common (popmax 48.4%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with Meester-Loeys syndrome.

What condition is associated with BGN p.Ser180= (c.540C>T)?

BGN p.Ser180= (c.540C>T) is associated with Meester-Loeys syndrome, X-linked spondyloepimetaphyseal dysplasia (ClinVar).

BGN p.Ser180=

Q: How common is BGN p.Ser180= (c.540C>T) in the general population?

BGN p.Ser180= (c.540C>T) is common (popmax 48.4%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.540C>T · rs1126499 · VCV1166521

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Common

common (popmax 48.4%, nfe) — too common for a highly-penetrant pathogenic allele

Conditions

Meester-Loeys syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP -13	GERP -3.8
Overall
CADD	1.026	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 48.4% European (non-Finnish) · 433,333/894,415 alleles

Filtering AF 48.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 48.3%

Overall 45.4% 548,673/1,208,518 alleles · common

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	48.4%	2
Finnishnot grpmax-eligible	46%	2
Middle Eastern	44.1%	2
Remaining individualsnot grpmax-eligible	44%	2
South Asian	40.9%	2
Ashkenazi Jewishnot grpmax-eligible	39.4%	3
East Asian	39.1%	3
Admixed American	38%	3
Amishnot grpmax-eligible	35.8%	3
African / African-American	15%	7

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.Ser180=
Coding: c.540C>T
MANE Select: NM_001711
dbSNP: rs1126499
Type: single nucleotide variant
Location: chrX:153506051 (GRCh38)
Structure: AlphaFold pLDDT 85.72

Full BGN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Meester-Loeys syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: X-linked spondyloepimetaphyseal dysplasia

Similar variants

BGN p.Ser180Gly Uncertain significance ★★ ⚠ same residue
BGN c.770+1G>A Likely pathogenic ★★ same condition
BGN p.Gln75Ter Pathogenic/Likely pathogenic ★★ same condition
BGN p.Trp25Ter Likely pathogenic ★★ same condition
BGN p.Arg214Cys Uncertain significance ★★ ⚠ same condition
BGN p.Arg6His Uncertain significance ★★ ⚠ same condition
BGN p.Gly66Ser Uncertain significance ★★ ⚠ same condition
BGN p.Met62Thr 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-ser180 (accessed [today's date]).

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