PSMC3 p.Ala241=
c.723C>T · rs148054958 · VCV3025494
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
rare (popmax 0.608%, afr)
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 -4.4 | GERP -4.7 |
| Overall | ||
| CADD | 2.671 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.608%
African / African-American · 456/74,960 alleles
Filtering AF
0.562%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.544%
Overall
0.0382%
615/1,611,312 alleles · rare
exomes 331/1,459,056 · genomes 284/152,256 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.608% | 164 |
| Middle Eastern | 0.0662% | 1,512 |
| Remaining individualsnot grpmax-eligible | 0.0641% | 1,560 |
| Admixed American | 0.0636% | 1,572 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0204% | 4,898 |
| South Asian | 0.00551% | 18,155 |
| European (non-Finnish) | 0.00543% | 18,412 |
| Finnishnot grpmax-eligible | 0.00313% | 31,957 |
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
- PSMC3
- Protein
- p.Ala241=
- Coding
- c.723C>T
- MANE Select
- NM_002804
- dbSNP
- rs148054958
- Type
- single nucleotide variant
- Location
- chr11:47422842 (GRCh38)
- Gene constraint
- LOEUF 0.352 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 80.58 · 139 PDB
- Residue 241
- an α-helix
Similar variants
- PSMC3 p.Ile261Thr Pathogenic ★★ same type
- PSMC3 p.Lys276Glu Uncertain significance ★★ ⚠ same type
- PSMC3 p.His417= Likely benign ★★ same type
- PSMC3 p.Arg304Gly Pathogenic ★ same type
- PSMC3 p.Arg304Trp Pathogenic ★ same type
- PSMC3 p.Lys155Arg Likely pathogenic ★ same type
- PSMC3 p.Met259Ile Pathogenic ★ same type
- PSMC3 p.Met310Thr Likely pathogenic ★ 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/psmc3-p-ala241 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown