MDH2 p.Val64=
c.192G>A · rs77424348 · VCV714349
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.74%, afr)
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 2.5 | phastCons 1 |
| Overall | ||
| CADD | 8.14 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.74%
African / African-American · 2,056/75,014 alleles
Filtering AF
2.64%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.6%
Overall
0.146%
2,350/1,614,014 alleles · low-frequency
exomes 1,137/1,461,772 · genomes 1,213/152,242 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 2.74% | 36 |
| Admixed American | 0.212% | 472 |
| Remaining individualsnot grpmax-eligible | 0.208% | 481 |
| Middle Eastern | 0.0825% | 1,212 |
| South Asian | 0.00549% | 18,212 |
| European (non-Finnish) | 0.00229% | 43,703 |
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
- MDH2
- Protein
- p.Val64=
- Coding
- c.192G>A
- MANE Select
- NM_005918
- dbSNP
- rs77424348
- Type
- single nucleotide variant
- Location
- chr7:76054955 (GRCh38)
- Gene constraint
- LOEUF 0.984 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.49 · 7 PDB
- Residue 64
- an α-helix
Similar variants
- MDH2 p.Val64Ala Uncertain significance ★★ ⚠ same residue
- MDH2 p.Val64Gly Uncertain significance ★ ⚠ same residue
- MDH2 p.Val64Met Uncertain significance ★ ⚠ same residue
- MDH2 p.Pro133Leu Pathogenic/Likely pathogenic ★★ same type
- MDH2 c.555+3A>G Uncertain significance ★★ same type
- MDH2 p.Ala126Thr Uncertain significance ★★ ⚠ same type
- MDH2 p.Ala135Gly Uncertain significance ★★ ⚠ same type
- MDH2 p.Ala141Thr 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/mdh2-p-val64 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown