H6PD p.Phe253=
c.759C>T · VCV4750424
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000254%, 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 3.9 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 10.27 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,180,048 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000186%
3/1,614,240 alleles · very rare
exomes 3/1,461,888 · genomes 0/152,352 · 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
- H6PD
- Protein
- p.Phe253=
- Coding
- c.759C>T
- MANE Select
- NM_004285
- Type
- single nucleotide variant
- Location
- chr1:9262072 (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 253
- the 'hexose-6-phosphate dehydrogenase' region; a turn
Similar variants
- 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
- H6PD p.Arg250His 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-phe253 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown