MDH2 p.Phe180=
c.540T>C · rs374801532 · VCV1747370
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00223%, eas)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -2.9 | |
| Overall | ||
| CADD | 5.906 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00223%
East Asian · 1/44,882 alleles
Overall
6.2e-05%
1/1,614,162 alleles · very rare
exomes 1/1,461,872 · genomes 0/152,290 · 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.Phe180=
- Coding
- c.540T>C
- MANE Select
- NM_005918
- dbSNP
- rs374801532
- Type
- single nucleotide variant
- Location
- chr7:76060483 (GRCh38)
- Gene constraint
- LOEUF 0.984 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.49 · 7 PDB
- Residue 180
- an α-helix
Similar variants
- MDH2 p.Phe180Ser Uncertain significance ★ ⚠ same residue
- MDH2 p.Ala135Gly Uncertain significance ★★ ⚠ same condition
- MDH2 p.Ala141Thr Uncertain significance ★★ same condition
- MDH2 p.Ala177Thr Uncertain significance ★★ ⚠ same condition
- MDH2 p.Ala21Val Uncertain significance ★★ ⚠ same condition
- MDH2 p.Ala242Val Uncertain significance ★★ ⚠ same condition
- MDH2 p.Ala256Thr Uncertain significance ★★ ⚠ same condition
- MDH2 p.Ala325Val Uncertain significance ★★ ⚠ same condition
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-phe180 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown