Is SUCLA2 p.Arg284= (c.852C>T) pathogenic?

SUCLA2 p.Arg284= (c.852C>T) is classified Likely benign in SUCLA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-09-14). Ultra-rare (popmax 0.0307%, afr); Associated with mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria.

How common is SUCLA2 p.Arg284= (c.852C>T) in the general population?

SUCLA2 p.Arg284= (c.852C>T) is ultra-rare (popmax 0.0307%, afr) (gnomAD).

SUCLA2 p.Arg284=

Q: What condition is associated with SUCLA2 p.Arg284= (c.852C>T)?

SUCLA2 p.Arg284= (c.852C>T) 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.852C>T · rs150191407 · VCV2716535

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0307%, afr)

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.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.32	GERP -1.2, phastCons 0.96
Overall
CADD	7.094	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0307% African / African-American · 23/74,990 alleles

Filtering AF 0.021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0178%

Overall 0.00167% 27/1,613,804 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0307%	3,260
Remaining individualsnot grpmax-eligible	0.0048%	20,832
South Asian	0.0011%	91,070

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.Arg284=
Coding: c.852C>T
MANE Select: NM_003850
dbSNP: rs150191407
Type: single nucleotide variant
Location: chr13:47954508 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.45 · 2 PDB
Residue 284: the atp-grasp domain; a UniProt-annotated variant site (in mtdps5); an α-helix

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 p.Arg284Cys Pathogenic/Likely pathogenic ★★ same residue
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.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-arg284 (accessed [today's date]).

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