Is BGN p.Arg358Ser (c.1072C>A) pathogenic?

BGN p.Arg358Ser (c.1072C>A) is classified Uncertain significance in BGN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-04). AlphaMissense: likely pathogenic (0.9078); Very rare (popmax 0.000223%, nfe).

How common is BGN p.Arg358Ser (c.1072C>A) in the general population?

BGN p.Arg358Ser (c.1072C>A) is very rare (popmax 0.000223%, nfe) (gnomAD).

What do computational predictors say about BGN p.Arg358Ser (c.1072C>A)?

AlphaMissense predicts likely pathogenic (score 0.9078) — an in-silico prediction, not a clinical call.

BGN p.Arg358Ser

c.1072C>A · rs1435587833 · VCV1964501

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9078 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000223%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9078	likely pathogenic
REVEL	0.249	benign-leaning
SaProt	LLR -6.99	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 3,810 bp · p 0.25 · regional, not allelic
Overall
CADD	27.9	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 0.000223% European (non-Finnish) · 2/895,601 alleles

Filtering AF 3.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.4e-05%

Overall 0.000248% 3/1,212,067 alleles · very rare exomes 3/1,097,876 · genomes 0/114,191 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0021%	47,650
European (non-Finnish)grpmax	0.000223%	447,800

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg358Ser
Coding: c.1072C>A
MANE Select: NM_001711
dbSNP: rs1435587833
Type: single nucleotide variant
Location: chrX:153508410 (GRCh38)
Structure: AlphaFold pLDDT 85.72

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

Similar variants

BGN p.Arg358His Uncertain significance ★★ ⚠ same residue
BGN p.Arg358Gly Uncertain significance ★ ⚠ same residue
BGN p.Arg358Leu 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

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-arg358ser (accessed [today's date]).

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