MDH2 p.Pro143=
c.429G>A · rs11538801 · VCV1673616
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 5 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.7%, sas)
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 1.3 | phastCons 1 |
| Overall | ||
| CADD | 17.46 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.7%
South Asian · 3,370/91,048 alleles
Filtering AF
3.6%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.55%
Overall
1.48%
23,886/1,611,256 alleles · low-frequency
exomes 22,074/1,458,898 · genomes 1,812/152,358 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 3.7% | 27 |
| Middle Eastern | 2.88% | 35 |
| Admixed American | 2.47% | 40 |
| Remaining individualsnot grpmax-eligible | 1.5% | 67 |
| European (non-Finnish) | 1.42% | 70 |
| Finnishnot grpmax-eligible | 1.16% | 86 |
| Ashkenazi Jewishnot grpmax-eligible | 0.977% | 102 |
| African / African-American | 0.236% | 424 |
| East Asian | 0.0156% | 6,406 |
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.Pro143=
- Coding
- c.429G>A
- MANE Select
- NM_005918
- dbSNP
- rs11538801
- Type
- single nucleotide variant
- Location
- chr7:76058078 (GRCh38)
- Gene constraint
- LOEUF 0.984 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.49 · 7 PDB
Similar variants
- MDH2 p.Pro143Leu Uncertain significance ★★ ⚠ same residue
- MDH2 p.Pro143Ala 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-pro143 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown