Is BGN p.Arg257Ser (c.771G>C) pathogenic?

BGN p.Arg257Ser (c.771G>C) is classified Uncertain significance in BGN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-23). AlphaMissense: likely pathogenic (0.9962); Very rare (popmax 0.000112%, nfe).

How common is BGN p.Arg257Ser (c.771G>C) in the general population?

BGN p.Arg257Ser (c.771G>C) is very rare (popmax 0.000112%, nfe) (gnomAD).

What do computational predictors say about BGN p.Arg257Ser (c.771G>C)?

AlphaMissense predicts likely pathogenic (score 0.9962) — an in-silico prediction, not a clinical call.

BGN p.Arg257Ser

c.771G>C · rs2521220779 · VCV2439512

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9962 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000112%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9962	likely pathogenic
REVEL	0.386	indeterminate
SaProt	LLR -8.38	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.9	GERP -0.24, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,810 bp · p 0.25 · regional, not allelic
Overall
CADD	22.5	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 0.000112% European (non-Finnish) · 1/894,395 alleles

Overall 9.12e-05% 1/1,096,288 alleles · very rare

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.Arg257Ser
Coding: c.771G>C
MANE Select: NM_001711
dbSNP: rs2521220779
Type: single nucleotide variant
Location: chrX:153507047 (GRCh38)
Structure: AlphaFold pLDDT 85.72

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

Similar variants

BGN p.Arg257Trp Uncertain significance ★ ⚠ 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-arg257ser (accessed [today's date]).

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