Is MDH2 p.Ile150Met (c.450C>G) pathogenic?

MDH2 p.Ile150Met (c.450C>G) is classified Uncertain significance in MDH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-13). AlphaMissense: ambiguous (0.5026); Absent from gnomAD v4.1.

How common is MDH2 p.Ile150Met (c.450C>G) in the general population?

MDH2 p.Ile150Met (c.450C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MDH2 p.Ile150Met (c.450C>G)?

AlphaMissense predicts ambiguous (score 0.5026) — an in-silico prediction, not a clinical call.

MDH2 p.Ile150Met

c.450C>G · rs1797911624 · VCV1953342

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5026 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5026	ambiguous
REVEL	0.773	moderately pathogenic-leaning
SaProt	LLR -12.21	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense is indeterminate.
Splicing
SpliceAI	Δ0.23	acceptor loss, 8 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.61	phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.54 · regional, not allelic
Overall
CADD	22.3	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MDH2
Protein: p.Ile150Met
Coding: c.450C>G
MANE Select: NM_005918
dbSNP: rs1797911624
Type: single nucleotide variant
Location: chr7:76060393 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.49 · 7 PDB
Residue 150: an α-helix

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

Similar variants

MDH2 p.Ile150Asn 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
MDH2 p.Ala21Val 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-ile150met (accessed [today's date]).

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