SUCLG1

Chr 2AR

succinate-CoA ligase GDP/ADP-forming subunit alpha

Also known as: GALPHA, MTDPS9, SUCLA1

The protein encodes the alpha subunit of succinate coenzyme A ligase, a mitochondrial enzyme that catalyzes the conversion of succinyl CoA and ADP/GDP to succinate and ATP/GTP in the citric acid cycle. Mutations cause mitochondrial DNA depletion syndrome 9, an autosomal recessive disorder characterized by encephalomyopathy with methylmalonic aciduria and fatal infantile lactic acidosis. The pathogenic mechanism involves mitochondrial dysfunction leading to impaired energy metabolism and secondary mitochondrial DNA depletion.

GeneReviewsOMIMResearchSummary from RefSeq, OMIM, UniProt, Mechanism
LOFmechanismARLOEUF 0.881 OMIM phenotype
Clinical SummarySUCLG1
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Gene-Disease Validity (ClinGen)
Leigh syndrome · ARModerate

Moderate evidence — consider for supplementary testing

Population Constraint (gnomAD)
Low constraint (pLI 0.00) — loss-of-function variants are relatively tolerated in the population.
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ClinVar Variants
47 unique Pathogenic / Likely Pathogenic· 142 VUS of 395 total submissions
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Clinical Trials
1 active or recruiting trial — potential therapeutic options may be available
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GeneReview available — SUCLG1
Authoritative clinical overview · Recommended first read
Open GeneReview ↗

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

Tolerant — LoF & missense variants common in population
LoF Constraint
0.88LOEUF
pLI 0.000
Z-score 1.94
OE 0.49 (0.280.88)
Tolerant

Typical tolerance to LoF variation

Missense Constraint
-0.22Z-score
OE missense 1.04 (0.931.18)
199 obs / 190.6 exp
Tolerant

Tolerant to missense variation

Observed / Expected Ratios
LoF OE0.49 (0.280.88)
00.351.4
Missense OE1.04 (0.931.18)
00.61.4
Synonymous OE1.02
01.21.6
LoF obs/exp: 8 / 16.5Missense obs/exp: 199 / 190.6Syn Z: -0.13
Curated Mechanism (G2P)Gene2Phenotype (DDG2P) ↗
definitiveSUCLG1-related fatal infantile lactic acidosisLOFAR

Predictions shown for reference only — model trained on dominant genes, not applicable to AR conditions.

DN
0.78top 25%
GOF
0.6248th %ile
LOF
0.3259th %ile

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

395 submitted variants in ClinVar

Classification Summary

Pathogenic35
Likely Pathogenic12
VUS142
Likely Benign150
Benign28
Conflicting20
35
Pathogenic
12
Likely Pathogenic
142
VUS
150
Likely Benign
28
Benign
20
Conflicting

Curated Variants Distribution

Classified variants from ClinVar · 5 ACMG categories

ClassificationLoFMissense + InframeNon-codingSynonymousTotal
Pathogenic
18
4
13
0
35
Likely Pathogenic
5
5
2
0
12
VUS
0
124
15
3
142
Likely Benign
0
3
80
67
150
Benign
0
0
28
0
28
Conflicting
20
Total2313613870387

LoF = frameshift, stop gained/lost, canonical splice · Counts from ClinVar esearch · Updated hourly

View in ClinVar →

Protein Context — Lollipop Plot

SUCLG1 · protein map & ClinVar variants

Showing all ClinVar variants across the protein. Search a specific variant to highlight its position.

3D Protein StructureAlphaFold
Clinical Literature
Open Research Assistant →