Is SUCLA2 p.Phe6= (c.18C>T) pathogenic?

SUCLA2 p.Phe6= (c.18C>T) is classified Likely benign in SUCLA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-07). Very rare (popmax 0.00112%, sas); Associated with mitochondrial DNA depletion syndrome, encephalomyopathic form with methylmalonic aciduria.

How common is SUCLA2 p.Phe6= (c.18C>T) in the general population?

SUCLA2 p.Phe6= (c.18C>T) is very rare (popmax 0.00112%, sas) (gnomAD).

SUCLA2 p.Phe6=

Q: What condition is associated with SUCLA2 p.Phe6= (c.18C>T)?

SUCLA2 p.Phe6= (c.18C>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.18C>T · rs1324839732 · VCV2728455

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00112%, sas)

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 0.3	GERP -4.6, phastCons 0.96
Overall
CADD	6.859	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00112% South Asian · 1/89,434 alleles

Overall 6.89e-05% 1/1,452,078 alleles · very rare

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.Phe6=
Coding: c.18C>T
MANE Select: NM_003850
dbSNP: rs1324839732
Type: single nucleotide variant
Location: chr13:48001252 (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-phe6 (accessed [today's date]).

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