Is BPGM p.Arg39Trp (c.115C>T) pathogenic?

BPGM p.Arg39Trp (c.115C>T) is classified Uncertain significance in BPGM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-29). AlphaMissense: likely benign (0.2045); Very rare (popmax 0.00223%, eas).

How common is BPGM p.Arg39Trp (c.115C>T) in the general population?

BPGM p.Arg39Trp (c.115C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BPGM p.Arg39Trp (c.115C>T)?

AlphaMissense predicts likely benign (score 0.2045) — an in-silico prediction, not a clinical call.

BPGM p.Arg39Trp

c.115C>T · VCV3379791

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2045 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2045	likely benign
REVEL	0.447	indeterminate
SaProt	LLR -13.02	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.1	GERP 0.48, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 18 kb · p 0.01 · 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 0.00223% East Asian · 1/44,870 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000682% 11/1,614,070 alleles · very rare exomes 11/1,461,862 · genomes 0/152,208 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,870
Admixed American	0.00167%	59,994
Finnishnot grpmax-eligible	0.00156%	64,022
European (non-Finnish)	0.000678%	147,502

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: BPGM
Protein: p.Arg39Trp
Coding: c.115C>T
MANE Select: NM_001724
Type: single nucleotide variant
Location: chr7:134661622 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.81 · 17 PDB
Residue 39: an α-helix

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

Similar variants

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BPGM p.His198Gln Uncertain significance ★★ ⚠ same type
BPGM p.Arg62= Likely benign ★★ same type
BPGM p.Leu162= Likely benign ★★ same type
BPGM p.Arg90Cys Pathogenic ★ same type
BPGM p.Ala243Val Uncertain significance ★ ⚠ same type
BPGM p.Ala244Val 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/bpgm-p-arg39trp (accessed [today's date]).

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