Is BPGM p.Arg172Met (c.515G>T) pathogenic?

BPGM p.Arg172Met (c.515G>T) is classified Uncertain significance in BPGM (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-19). AlphaMissense: likely benign (0.2103); Very rare (popmax 0.00127%, nfe).

How common is BPGM p.Arg172Met (c.515G>T) in the general population?

BPGM p.Arg172Met (c.515G>T) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about BPGM p.Arg172Met (c.515G>T)?

AlphaMissense predicts likely benign (score 0.2103) — an in-silico prediction, not a clinical call.

BPGM p.Arg172Met

c.515G>T · rs778462618 · VCV2613361

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2103 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2103	likely benign
REVEL	0.287	benign-leaning
SaProt	LLR -10.52	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 8.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 18 kb · p 0.01 · 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 0.00127% European (non-Finnish) · 15/1,180,022 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000929% 15/1,614,024 alleles · very rare exomes 12/1,461,852 · genomes 3/152,172 · 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: BPGM
Protein: p.Arg172Met
Coding: c.515G>T
MANE Select: NM_001724
dbSNP: rs778462618
Type: single nucleotide variant
Location: chr7:134662022 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.81 · 17 PDB
Residue 172: an α-helix

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

Similar variants

BPGM p.Glu176Lys Uncertain significance ★★ ⚠ same type
BPGM p.His11Asn Uncertain significance ★★ ⚠ same type
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-arg172met (accessed [today's date]).

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