Is BPGM p.Arg21fs (c.61del) pathogenic?

BPGM p.Arg21fs (c.61del) is classified Pathogenic in BPGM (ClinVar, No assertion criteria, 1 submitter; last evaluated 1992-11-15). Very rare (popmax 8.47e-05%, nfe); Associated with hemolytic anemia due to diphosphoglycerate mutase deficiency.

What condition is associated with BPGM p.Arg21fs (c.61del)?

BPGM p.Arg21fs (c.61del) is associated with hemolytic anemia due to diphosphoglycerate mutase deficiency (ClinVar).

How common is BPGM p.Arg21fs (c.61del) in the general population?

BPGM p.Arg21fs (c.61del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

BPGM p.Arg21fs

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.61del · rs786205092 · VCV12092

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

hemolytic anemia due to diphosphoglycerate mutase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 2 of 3
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 11	GERP 2.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,008 alleles

Overall 6.2e-05% 1/1,614,156 alleles · very rare exomes 1/1,461,866 · genomes 0/152,290 · 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.Arg21fs
Coding: c.61del
MANE Select: NM_001724
dbSNP: rs786205092
Type: Deletion
Location: chr7:134661567 (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.Arg21His Uncertain significance ★ ⚠ same residue
BPGM p.Arg90Cys Pathogenic ★ same condition
BPGM p.Arg154Gln 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

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-arg21fs (accessed [today's date]).

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