IDH3A p.Pro74=
c.222T>C · rs2548836495 · VCV2831322
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
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 -14 | GERP -4.1 |
| Overall | ||
| CADD | 0.121 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,712 alleles
Overall
6.2e-05%
1/1,613,818 alleles · very rare
exomes 1/1,461,510 · genomes 0/152,308 · 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
- IDH3A
- Protein
- p.Pro74=
- Coding
- c.222T>C
- MANE Select
- NM_005530
- dbSNP
- rs2548836495
- Type
- single nucleotide variant
- Location
- chr15:78160139 (GRCh38)
- Gene constraint
- LOEUF 1.09 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.83 · 19 PDB
Similar variants
- IDH3A c.289+3A>G Uncertain significance ★★ same type
- IDH3A p.Ala122Val Uncertain significance ★★ ⚠ same type
- IDH3A p.Ala197Val Uncertain significance ★★ ⚠ same type
- IDH3A p.Ala330Val Uncertain significance ★★ ⚠ same type
- IDH3A p.Ala5Ser Uncertain significance ★★ ⚠ same type
- IDH3A p.Arg178Cys Uncertain significance ★★ ⚠ same type
- IDH3A p.Arg188Trp Uncertain significance ★★ same type
- IDH3A p.Arg361Ter 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/idh3a-p-pro74 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown