Is BGN p.Pro18Ser (c.52C>T) pathogenic?

BGN p.Pro18Ser (c.52C>T) is classified Uncertain significance in BGN (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-25). AlphaMissense: likely pathogenic (0.7432); Ultra-rare (popmax 0.0348%, amr).

How common is BGN p.Pro18Ser (c.52C>T) in the general population?

BGN p.Pro18Ser (c.52C>T) is ultra-rare (popmax 0.0348%, amr) (gnomAD).

What do computational predictors say about BGN p.Pro18Ser (c.52C>T)?

AlphaMissense predicts likely pathogenic (score 0.7432) — an in-silico prediction, not a clinical call.

BGN p.Pro18Ser

c.52C>T · rs1305457220 · VCV1925100

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7432 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0348%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.7432	likely pathogenic
REVEL	0.598	indeterminate
SaProt	LLR -6.63	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,810 bp · p 0.25 · regional, not allelic
Overall
CADD	26.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0348% Admixed American · 16/45,973 alleles

Filtering AF 0.0218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00132% 16/1,210,522 alleles · ultra-rare exomes 6/1,097,698 · genomes 10/112,824 · 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.Pro18Ser
Coding: c.52C>T
MANE Select: NM_001711
dbSNP: rs1305457220
Type: single nucleotide variant
Location: chrX:153504683 (GRCh38)
Structure: AlphaFold pLDDT 85.72

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

Similar variants

BGN p.Pro18= Likely benign ★ same residue
BGN c.770+1G>A Likely pathogenic ★★ same type
BGN p.Gln75Ter Pathogenic/Likely pathogenic ★★ same type
BGN p.Trp25Ter Likely pathogenic ★★ same type
BGN c.909+4A>G Uncertain significance ★★ same type
BGN p.Ala330Asp Uncertain significance ★★ ⚠ same type
BGN p.Ala330Pro Uncertain significance ★★ ⚠ same type
BGN p.Ala41Ser Uncertain significance ★★ ⚠ same type

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-pro18ser (accessed [today's date]).

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