GPX4 p.Ser45=
c.135C>T · rs372370002 · VCV1661361
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0206%, nfe)
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 -2.8 | GERP -2.1 |
| Overall | ||
| CADD | 6.742 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0206%
European (non-Finnish) · 243/1,179,914 alleles
Filtering AF
0.0184%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0176%
Overall
0.0157%
253/1,613,102 alleles · ultra-rare
exomes 222/1,460,750 · genomes 31/152,352 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0206% | 4,856 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,622 |
| African / African-American | 0.00533% | 18,766 |
| Admixed American | 0.00333% | 30,014 |
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
- GPX4
- Protein
- p.Ser45=
- Coding
- c.135C>T
- MANE Select
- NM_002085
- dbSNP
- rs372370002
- Type
- single nucleotide variant
- Location
- chr19:1105236 (GRCh38)
- Gene constraint
- LOEUF 1.385 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Residue 45
- a β-strand
Similar variants
- GPX4 p.Arg179His Likely pathogenic ★★ same type
- GPX4 c.85-258C>T Uncertain significance ★★ same type
- GPX4 c.85-307C>T Uncertain significance ★★ same type
- GPX4 c.85-408G>C Uncertain significance ★★ same type
- GPX4 c.85-420G>A Uncertain significance ★★ same type
- GPX4 c.85-427C>T Uncertain significance ★★ same type
- GPX4 c.85-429C>T Uncertain significance ★★ same type
- GPX4 p.Ala120Thr 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/gpx4-p-ser45 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown