PSPH p.Glu222=
c.666A>G · rs1584363520 · VCV741327
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000425%, 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 -2.1 | GERP -2.5 |
| Overall | ||
| CADD | 0.115 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000425%
European (non-Finnish) · 5/1,177,626 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.00031%
5/1,611,474 alleles · very rare
exomes 5/1,459,192 · genomes 0/152,282 · 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
- PSPH
- Protein
- p.Glu222=
- Coding
- c.666A>G
- MANE Select
- NM_004577
- dbSNP
- rs1584363520
- Type
- single nucleotide variant
- Location
- chr7:56011774 (GRCh38)
- Gene constraint
- LOEUF 1.063 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 92.88 · 6 PDB
- Residue 222
- an α-helix
Similar variants
- PSPH p.Arg101Ter Likely pathogenic ★★ same type
- PSPH c.422-3A>C Uncertain significance ★★ same type
- PSPH c.570+3A>G Uncertain significance ★★ same type
- PSPH c.570+5G>C Uncertain significance ★★ same type
- PSPH c.*341G>A Uncertain significance ★★ same type
- PSPH p.Asn124Ser Uncertain significance ★★ ⚠ same type
- PSPH p.Asp32Asn Uncertain significance ★★ ⚠ same type
- PSPH p.Gln204His 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/psph-p-glu222 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown