Is GPI p.Pro201= (c.603C>G) pathogenic?

GPI p.Pro201= (c.603C>G) is classified Benign/Likely benign in GPI (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-03-01). Rare (popmax 0.554%, nfe); Associated with hemolytic anemia due to glucophosphate isomerase deficiency.

What condition is associated with GPI p.Pro201= (c.603C>G)?

GPI p.Pro201= (c.603C>G) is associated with hemolytic anemia due to glucophosphate isomerase deficiency (ClinVar).

How common is GPI p.Pro201= (c.603C>G) in the general population?

GPI p.Pro201= (c.603C>G) is rare (popmax 0.554%, nfe) (gnomAD).

GPI p.Pro201=

Q: How is Hemolytic anemia due to glucophosphate isomerase deficiency inherited?

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

c.603C>G · rs1062480 · VCV780175

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.554%, nfe)

Conditions

hemolytic anemia due to glucophosphate isomerase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -4.5
Overall
CADD	0.035	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.554% European (non-Finnish) · 6,534/1,179,996 alleles

Filtering AF 0.543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.538%

Overall 0.442% 7,140/1,614,112 alleles · rare exomes 6,698/1,461,850 · genomes 442/152,262 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	0.769%	130
European (non-Finnish)grpmax	0.554%	181
Remaining individualsnot grpmax-eligible	0.446%	224
Ashkenazi Jewishnot grpmax-eligible	0.196%	510
Admixed American	0.113%	882
African / African-American	0.0959%	1,042
South Asian	0.0878%	1,138
Middle Eastern	0.0825%	1,212
Finnishnot grpmax-eligible	0.0578%	1,731

Amish 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: GPI
Protein: p.Pro201=
Coding: c.603C>G
MANE Select: NM_000175
dbSNP: rs1062480
Type: single nucleotide variant
Location: chr19:34377851 (GRCh38)
Structure: AlphaFold pLDDT 93.81 · 1 PDB
Residue 201: a β-strand

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

Disease context

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

For Hemolytic anemia due to glucophosphate isomerase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

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GPI p.Arg347Cys Pathogenic/Likely pathogenic ★★ same condition
GPI p.Arg347His Pathogenic/Likely pathogenic ★★ ⚠ same condition
GPI p.Arg446Ter Pathogenic/Likely pathogenic ★★ same condition
GPI p.Arg472Cys Pathogenic ★★ ⚠ same condition
GPI p.Arg96Ter Pathogenic/Likely pathogenic ★★ same condition
GPI p.Gln343Arg Pathogenic/Likely pathogenic ★★ same condition
GPI p.Ala350Thr Uncertain significance ★★ ⚠ 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/gpi-p-pro201 (accessed [today's date]).

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