H6PD p.Pro554=
c.1662G>A · rs369428059 · VCV1555322
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.028%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -10 | GERP -4.4 |
| Overall | ||
| CADD | 0.082 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.028%
European (non-Finnish) · 330/1,179,542 alleles
Filtering AF
0.0255%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0245%
Overall
0.0227%
366/1,613,028 alleles · ultra-rare
exomes 349/1,460,822 · genomes 17/152,206 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.028% | 3,574 |
| Finnishnot grpmax-eligible | 0.0173% | 5,779 |
| African / African-American | 0.0133% | 7,492 |
| Remaining individualsnot grpmax-eligible | 0.00801% | 12,490 |
| South Asian | 0.00769% | 13,011 |
| East Asian | 0.00446% | 22,440 |
| Admixed American | 0.00167% | 60,010 |
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
- H6PD
- Protein
- p.Pro554=
- Coding
- c.1662G>A
- MANE Select
- NM_004285
- dbSNP
- rs369428059
- Type
- single nucleotide variant
- Location
- chr1:9264155 (GRCh38)
- Gene constraint
- LOEUF 1.011 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 90.89 · 1 PDB
- Residue 554
- a UniProt-annotated variant site (in cortrd1; loss of glucose-6-phosphate dehydrogenase activity); a UniProt-annotated variant site (in); the '6-phosphogluconolactonase' region
Similar variants
- H6PD p.Pro554Leu Benign ★★ same residue
- H6PD p.Tyr316Ter Pathogenic ★★ same type
- H6PD p.Ala286Val Uncertain significance ★★ ⚠ same type
- H6PD p.Ala299Val Uncertain significance ★★ ⚠ same type
- H6PD p.Ala338Thr Uncertain significance ★★ ⚠ same type
- H6PD p.Ala605Val Uncertain significance ★★ ⚠ same type
- H6PD p.Arg109His Uncertain significance ★★ ⚠ same type
- H6PD p.Arg250Cys 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/h6pd-p-pro554 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown