Is MDH2 p.Arg7Trp (c.19C>T) pathogenic?

MDH2 p.Arg7Trp (c.19C>T) is classified Uncertain significance in MDH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-22). AlphaMissense: likely pathogenic (0.6072); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MDH2 p.Arg7Trp (c.19C>T)?

MDH2 p.Arg7Trp (c.19C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MDH2 p.Arg7Trp (c.19C>T) in the general population?

MDH2 p.Arg7Trp (c.19C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MDH2 p.Arg7Trp (c.19C>T)?

AlphaMissense predicts likely pathogenic (score 0.6072) — an in-silico prediction, not a clinical call.

MDH2 p.Arg7Trp

c.19C>T · rs1163245053 · VCV2560376

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6072 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,536,556)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6072	likely pathogenic
REVEL	0.285	benign-leaning
SaProt	LLR -13.91	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 18 kb · p 0.54 · regional, not allelic
Overall
CADD	28.5	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

No allele count reported in gnomAD v4.1 (AN 1,536,556). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: MDH2
Protein: p.Arg7Trp
Coding: c.19C>T
MANE Select: NM_005918
dbSNP: rs1163245053
Type: single nucleotide variant
Location: chr7:76048179 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.49 · 7 PDB

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.Arg7Gln Uncertain significance ★★ ⚠ same residue
MDH2 p.Arg7Pro Uncertain significance ★★ ⚠ same residue
MDH2 p.Arg7= Likely benign ★ 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

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-arg7trp (accessed [today's date]).

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