PPARA p.Cys105=
c.315C>T · rs147010249 · VCV738459
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0775%, 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 -6.1 | |
| Overall | ||
| CADD | 6.515 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0775%
African / African-American · 58/74,880 alleles
Filtering AF
0.0614%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0557%
Overall
0.00651%
105/1,613,994 alleles · ultra-rare
exomes 68/1,461,874 · genomes 37/152,120 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.0775% | 1,291 |
| Admixed American | 0.0183% | 5,454 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,248 |
| East Asian | 0.00446% | 22,442 |
| South Asian | 0.0022% | 45,544 |
| European (non-Finnish) | 0.00186% | 53,638 |
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
- PPARA
- Protein
- p.Cys105=
- Coding
- c.315C>T
- MANE Select
- NM_005036
- dbSNP
- rs147010249
- Type
- single nucleotide variant
- Location
- chr22:46215279 (GRCh38)
- Gene constraint
- LOEUF 0.711 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 81.18 · 79 PDB
- Residue 105
- a DNA-binding region
Similar variants
- PPARA p.Asn235= Benign ★★ same type
- PPARA p.Leu184= Benign ★★ same type
- PPARA p.Val227Ala Benign ★★ same type
- PPARA p.Ala186Val Uncertain significance ★ same type
- PPARA p.Ala201Thr Uncertain significance ★ ⚠ same type
- PPARA p.Ala225Thr Uncertain significance ★ ⚠ same type
- PPARA p.Ala291Thr Uncertain significance ★ ⚠ same type
- PPARA p.Ala381Pro 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/ppara-p-cys105 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown