MDH2 p.Val237=
c.711G>A · VCV4777738
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.004%, afr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.46 | donor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.57 | phastCons 1 |
| Overall | ||
| CADD | 16.76 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.004%
African / African-American · 3/74,920 alleles
Filtering AF
0.00106%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000495%
Overall
0.000186%
3/1,613,368 alleles · very rare
exomes 1/1,461,212 · genomes 2/152,156 · 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
- MDH2
- Protein
- p.Val237=
- Coding
- c.711G>A
- MANE Select
- NM_005918
- Type
- single nucleotide variant
- Location
- chr7:76064416 (GRCh38)
- Gene constraint
- LOEUF 0.984 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.49 · 7 PDB
- Residue 237
- an α-helix
Similar variants
- MDH2 p.Val237Ala Uncertain significance ★ ⚠ same residue
- MDH2 p.Val237Met 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
- MDH2 p.Ala177Thr 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-val237 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown