SDHAF1
Chr 19ARsuccinate dehydrogenase complex assembly factor 1
Also known as: LYRM8, MC2DN2
The protein resides in the mitochondrial matrix and is essential for assembly of the succinate dehydrogenase (SDH) complex II of the mitochondrial respiratory chain, though it does not physically associate with the assembled complex. Mutations cause mitochondrial complex II deficiency (also called SDH-defective infantile leukoencephalopathy) through an autosomal recessive inheritance pattern. The pathogenic mechanism involves loss of function, preventing proper assembly of the SDH complex required for mitochondrial respiration.
Limited evidence — not for standalone diagnostic reporting
2 total gene-disease associations curated
Population Genetics & Constraint
gnomAD v4 — loss-of-function & missense intolerance
Highly tolerant — LoF variants common in population
Mild missense constraint
Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.
The Badonyi & Marsh prediction model was trained exclusively on dominant disease genes. Predictions are not reliable for genes with autosomal recessive inheritance and are shown at reduced opacity for reference only.
Predictions from Badonyi M, Marsh JA. PLoS ONE. 2024;19(8):e0307312.
ClinVar Variant Classifications
107 submitted variants in ClinVar
Classification Summary
Curated Variants Distribution
Classified variants from ClinVar · 5 ACMG categories
| Classification | LoF | Missense + Inframe | Non-coding | Synonymous | Total |
|---|---|---|---|---|---|
Pathogenic | 1 | 3 | 12 | 0 | 16 |
Likely Pathogenic | 2 | 1 | 0 | 0 | 3 |
VUS | 0 | 44 | 16 | 1 | 61 |
Likely Benign | 0 | 1 | 4 | 15 | 20 |
Benign | 0 | 1 | 3 | 0 | 4 |
Conflicting | — | 3 | |||
| Total | 3 | 50 | 35 | 16 | 107 |
LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly
View in ClinVar →Protein Context — Lollipop Plot
SDHAF1 · protein map & ClinVar variants
Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.
3D Protein StructureAlphaFold
External Resources
Links to major genomics databases and tools
Clinical Trials
Active and recruiting trials from ClinicalTrials.gov
No active trials found for this gene.
Search ClinicalTrials.gov →External Resources
Links to major genomics databases and tools