Is SUCLA2 p.Arg26= (c.78G>A) pathogenic?

SUCLA2 p.Arg26= (c.78G>A) is classified Likely benign in SUCLA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-30). Very rare (popmax 0.00187%, nfe); Associated with mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria.

How common is SUCLA2 p.Arg26= (c.78G>A) in the general population?

SUCLA2 p.Arg26= (c.78G>A) is very rare (popmax 0.00187%, nfe) (gnomAD).

SUCLA2 p.Arg26=

Q: What condition is associated with SUCLA2 p.Arg26= (c.78G>A)?

SUCLA2 p.Arg26= (c.78G>A) is associated with mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (ClinVar).

Q: How is Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria inherited?

Typically Mitochondrial inheritance (Orphanet). A genetic counselor can assess individual risk for a family.

c.78G>A · rs1174121047 · VCV537759

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00187%, nfe)

Conditions

mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.118	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.59	GERP -2.7, phastCons 0.13
Overall
CADD	6.605	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00187% European (non-Finnish) · 22/1,178,690 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00143% 23/1,609,564 alleles · very rare exomes 15/1,457,316 · genomes 8/152,248 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00187%	53,577
African / African-American	0.00134%	74,882

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SUCLA2
Protein: p.Arg26=
Coding: c.78G>A
MANE Select: NM_003850
dbSNP: rs1174121047
Type: single nucleotide variant
Location: chr13:48001192 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.45 · 2 PDB

Full SUCLA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria (Orphanet):

Inheritance: Mitochondrial inheritance
Onset: Infancy

Similar variants

SUCLA2 c.534+1G>A Pathogenic ★★ same condition
SUCLA2 p.Ala307Val Pathogenic/Likely pathogenic ★★ ⚠ same condition
SUCLA2 p.Arg160Ter Pathogenic/Likely pathogenic ★★ same condition
SUCLA2 p.Arg284Cys Pathogenic/Likely pathogenic ★★ same condition
SUCLA2 p.Asp333Gly Pathogenic/Likely pathogenic ★★ same condition
SUCLA2 p.Ala12Val Uncertain significance ★★ ⚠ same condition
SUCLA2 p.Ala27Val Uncertain significance ★★ ⚠ same condition
SUCLA2 p.Ala330Pro 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/sucla2-p-arg26 (accessed [today's date]).

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