Is BPGM p.Arg154Gln (c.461G>A) pathogenic?

BPGM p.Arg154Gln (c.461G>A) is classified Uncertain significance in BPGM (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-16). AlphaMissense: likely benign (0.1); Very rare (popmax 0.00329%, sas); Associated with hemolytic anemia due to diphosphoglycerate mutase deficiency.

What condition is associated with BPGM p.Arg154Gln (c.461G>A)?

BPGM p.Arg154Gln (c.461G>A) is associated with hemolytic anemia due to diphosphoglycerate mutase deficiency (ClinVar).

How common is BPGM p.Arg154Gln (c.461G>A) in the general population?

BPGM p.Arg154Gln (c.461G>A) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about BPGM p.Arg154Gln (c.461G>A)?

AlphaMissense predicts likely benign (score 0.1) — an in-silico prediction, not a clinical call.

BPGM p.Arg154Gln

Q: How is Hemolytic anemia due to diphosphoglycerate mutase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.461G>A · rs1206399907 · VCV2439542

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hemolytic anemia due to diphosphoglycerate mutase deficiency

Computational evidence

Protein change
AlphaMissense	0.1	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -9.00	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
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	14.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,078 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000434% 7/1,613,970 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,359
Remaining individualsnot grpmax-eligible	0.0016%	62,490
African / African-American	0.00134%	74,902
European (non-Finnish)	0.000169%	590,012

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.Arg154Gln
Coding: c.461G>A
MANE Select: NM_001724
dbSNP: rs1206399907
Type: single nucleotide variant
Location: chr7:134661968 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.81 · 17 PDB

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

Disease context

hemolytic anemia due to diphosphoglycerate mutase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hemolytic anemia due to diphosphoglycerate mutase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy

Similar variants

BPGM p.Arg154Leu Uncertain significance ★ ⚠ same residue
BPGM p.Arg90Cys Pathogenic ★ same condition
BPGM p.Arg21His Uncertain significance ★ ⚠ same condition
BPGM p.Arg227Cys Conflicting classifications of pathogenicity ★ ⚠ same condition
BPGM c.601+16A>G Likely benign ★ same condition
BPGM p.Arg62Gln Pathogenic same condition
BPGM p.Arg90His Pathogenic same condition
BPGM p.Arg21fs Pathogenic same condition

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-arg154gln (accessed [today's date]).

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