Is MDH2 p.Ile299fs (c.890dup) pathogenic?

MDH2 p.Ile299fs (c.890dup) is classified Uncertain significance in MDH2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-01). No allele count reported in gnomAD v4.1 (AN 1,606,994).

How common is MDH2 p.Ile299fs (c.890dup) in the general population?

MDH2 p.Ile299fs (c.890dup) is no allele count reported in gnomAD v4.1 (AN 1,606,994) (gnomAD).

MDH2 p.Ile299fs

c.890dup · VCV3646637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,606,994)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,606,994). 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.Ile299fs
Coding: c.890dup
MANE Select: NM_005918
Type: Duplication
Location: chr7:76066278 (GRCh38)
Gene constraint: LOEUF 0.984 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.49 · 7 PDB
Residue 299: a β-strand

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

Similar variants

MDH2 p.Ile299= Likely benign ★★ same residue
MDH2 p.Ile299Thr Uncertain significance ★ same residue
MDH2 p.Ser69fs Pathogenic ★ same type
MDH2 c.633+5dup Uncertain significance ★ same type
MDH2 p.Leu53fs Conflicting classifications of pathogenicity ★ same type
MDH2 c.734-4dup Benign ★ 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-ile299fs (accessed [today's date]).

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