Is MDH2 p.Ser250= (c.750C>T) pathogenic?

MDH2 p.Ser250= (c.750C>T) is classified Likely benign in MDH2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-03-23). Ultra-rare (popmax 0.0331%, mid); Associated with Inborn genetic diseases.

What condition is associated with MDH2 p.Ser250= (c.750C>T)?

MDH2 p.Ser250= (c.750C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MDH2 p.Ser250= (c.750C>T) in the general population?

MDH2 p.Ser250= (c.750C>T) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

MDH2 p.Ser250=

c.750C>T · rs782265872 · VCV795193

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

Conditions

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 0.87	phastCons 1
Overall
CADD	11.35	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0331% Middle Eastern · 2/6,034 alleles

Filtering AF 0.00584% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00243%

Overall 0.000496% 8/1,614,056 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0331%	3,017
European (non-Finnish)	0.000508%	196,669

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.Ser250=
Coding: c.750C>T
MANE Select: NM_005918
dbSNP: rs782265872
Type: single nucleotide variant
Location: chr7:76064818 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.49 · 7 PDB
Residue 250: an α-helix

Full MDH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MDH2 p.Ser250Phe 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-ser250 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown