PSME4 p.Pro830=
c.2490G>A · VCV3427069
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.126%, sas)
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 -5 | GERP -4.4 |
| Overall | ||
| CADD | 2.888 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.126%
South Asian · 114/90,750 alleles
Filtering AF
0.107%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0998%
Overall
0.0194%
313/1,611,582 alleles · rare
exomes 287/1,459,754 · genomes 26/151,828 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.126% | 796 |
| Middle Eastern | 0.0506% | 1,977 |
| Remaining individualsnot grpmax-eligible | 0.0433% | 2,311 |
| African / African-American | 0.0147% | 6,794 |
| Admixed American | 0.0134% | 7,462 |
| European (non-Finnish) | 0.012% | 8,303 |
| Finnishnot grpmax-eligible | 0.011% | 9,123 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,548 |
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
- PSME4
- Protein
- p.Pro830=
- Coding
- c.2490G>A
- MANE Select
- NM_014614
- Type
- single nucleotide variant
- Location
- chr2:53919177 (GRCh38)
- Gene constraint
- LOEUF 0.393 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 90.29 · 5 PDB
- Residue 830
- an α-helix
Similar variants
- PSME4 p.Ala1137Asp Uncertain significance ★ ⚠ same type
- PSME4 p.Ala120Thr Uncertain significance ★ ⚠ same type
- PSME4 p.Ala1622Ser Uncertain significance ★ ⚠ same type
- PSME4 p.Ala190Thr Uncertain significance ★ ⚠ same type
- PSME4 p.Arg1131Cys Uncertain significance ★ ⚠ same type
- PSME4 p.Arg1176Ile Uncertain significance ★ ⚠ same type
- PSME4 p.Arg1187Trp Uncertain significance ★ ⚠ same type
- PSME4 p.Arg121Cys 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/psme4-p-pro830 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown