PDHA2 p.Cys99=
c.297C>T · VCV4821224
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
low-frequency (popmax 1.11%, 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 -4.9 | GERP -3.8 |
| Overall | ||
| CADD | 0.439 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.11%
South Asian · 1,014/91,086 alleles
Filtering AF
1.06%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.03%
Overall
0.0696%
1,124/1,614,152 alleles · low-frequency
exomes 1,059/1,461,892 · genomes 65/152,260 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 1.11% | 90 |
| Remaining individualsnot grpmax-eligible | 0.0928% | 1,078 |
| Middle Eastern | 0.0165% | 6,062 |
| Admixed American | 0.015% | 6,670 |
| African / African-American | 0.00533% | 18,760 |
| East Asian | 0.00446% | 22,424 |
| European (non-Finnish) | 0.00305% | 32,779 |
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
- PDHA2
- Protein
- p.Cys99=
- Coding
- c.297C>T
- MANE Select
- NM_005390
- Type
- single nucleotide variant
- Location
- chr4:95840447 (GRCh38)
- Gene constraint
- LOEUF 1.406 · pLI 0.52 (gnomAD)
- Structure
- AlphaFold pLDDT 94.08
Similar variants
- PDHA2 p.Met227Val Likely pathogenic ★★ same type
- PDHA2 p.Ala173Gly Uncertain significance ★ ⚠ same type
- PDHA2 p.Ala18Pro Uncertain significance ★ ⚠ same type
- PDHA2 p.Ala18Val Uncertain significance ★ ⚠ same type
- PDHA2 p.Ala197Val Uncertain significance ★ ⚠ same type
- PDHA2 p.Ala32Val Uncertain significance ★ ⚠ same type
- PDHA2 p.Ala347Gly Uncertain significance ★ ⚠ same type
- PDHA2 p.Ala348Thr 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/pdha2-p-cys99 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown