Is BPGM p.Arg90His (c.269G>A) pathogenic?

BPGM p.Arg90His (c.269G>A) is classified Pathogenic in BPGM (ClinVar, No assertion criteria, 1 submitter; last evaluated 1992-11-15). AlphaMissense: likely pathogenic (0.8949); Very rare (popmax 0.00223%, eas); Associated with hemolytic anemia due to diphosphoglycerate mutase deficiency.

What condition is associated with BPGM p.Arg90His (c.269G>A)?

BPGM p.Arg90His (c.269G>A) is associated with hemolytic anemia due to diphosphoglycerate mutase deficiency (ClinVar).

How common is BPGM p.Arg90His (c.269G>A) in the general population?

BPGM p.Arg90His (c.269G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about BPGM p.Arg90His (c.269G>A)?

AlphaMissense predicts likely pathogenic (score 0.8949) — an in-silico prediction, not a clinical call.

BPGM p.Arg90His

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.269G>A · rs781222092 · VCV973178

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8949 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hemolytic anemia due to diphosphoglycerate mutase deficiency

Computational evidence

Protein change
AlphaMissense	0.8949	likely pathogenic ✓ concordant with ClinVar
REVEL	0.923	moderately pathogenic-leaning
SaProt	LLR -13.73	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 18 kb · p 0.01 · regional, not allelic
Overall
CADD	33.0	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 · 1/44,890 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000991% 16/1,614,010 alleles · very rare exomes 14/1,461,846 · genomes 2/152,164 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
East Asiangrpmax	0.00223%	44,890
South Asian	0.0011%	91,086
European (non-Finnish)	0.00102%	98,335

Ashkenazi Jewish 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: BPGM
Protein: p.Arg90His
Coding: c.269G>A
MANE Select: NM_001724
dbSNP: rs781222092
Type: single nucleotide variant
Location: chr7:134661776 (GRCh38)
Gene constraint: LOEUF 0.987 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 95.81 · 17 PDB
Residue 90: a UniProt-annotated variant site (in ecyt8; mutation identified at protein level; marked decrease in synthase and mutase activities; no effect on phosphatase activity); an α-helix; a binding site

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.Arg90Cys Pathogenic ★ same residue
BPGM p.Arg154Gln Uncertain significance ★ ⚠ 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.Arg21fs Pathogenic same condition
BPGM p.Glu176Lys 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-arg90his (accessed [today's date]).

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