IDH3A p.Ser288=
c.864G>A · rs575301725 · VCV1362881
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00134%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.94 | donor loss · deltas |
|---|---|---|
| Pangolin | Δ0.79 | loss · gain 0.47 · agrees with SpliceAI · independent |
| Constraint at this position | ||
| Conservation | phyloP 9.9 | GERP 2.1, phastCons 1 |
| Overall | ||
| CADD | 25.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00134%
African / African-American · 1/74,684 alleles
Filtering AF
8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.4e-05%
Overall
0.000311%
5/1,605,896 alleles · very rare
exomes 4/1,453,970 · genomes 1/151,926 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 0.00134% | 74,684 |
| European (non-Finnish) | 0.000341% | 293,199 |
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.Ser288=
- Coding
- c.864G>A
- MANE Select
- NM_005530
- dbSNP
- rs575301725
- Type
- single nucleotide variant
- Location
- chr15:78165076 (GRCh38)
- Gene constraint
- LOEUF 1.09 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.83 · 19 PDB
- Residue 288
- a UniProt-annotated variant site (in rp90)
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-ser288 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown