Is SDHA p.Asp394= (c.1182C>T) pathogenic?

SDHA p.Asp394= (c.1182C>T) is classified Benign/Likely benign in SDHA (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-11-03). Very rare (popmax 0.00891%, eas); Associated with mitochondrial complex II deficiency, nuclear type 1.

What condition is associated with SDHA p.Asp394= (c.1182C>T)?

SDHA p.Asp394= (c.1182C>T) is associated with mitochondrial complex II deficiency, nuclear type 1, pheochromocytoma/paraganglioma syndrome 5, hereditary neoplastic syndrome (ClinVar).

How common is SDHA p.Asp394= (c.1182C>T) in the general population?

SDHA p.Asp394= (c.1182C>T) is very rare (popmax 0.00891%, eas) (gnomAD).

How is Isolated succinate-CoQ reductase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

SDHA p.Asp394=

c.1182C>T · rs377317558 · VCV239637

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Conditions

mitochondrial complex II deficiency, nuclear type 1

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 -4.7	GERP -3.5
Overall
CADD	2.202	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00891% East Asian · 4/44,878 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000805% 13/1,614,032 alleles · very rare exomes 10/1,461,792 · genomes 3/152,240 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00891%	11,220
South Asian	0.0022%	45,537
Admixed American	0.00167%	60,016
Finnishnot grpmax-eligible	0.00156%	64,030
European (non-Finnish)	0.000424%	235,990

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: SDHA
Protein: p.Asp394=
Coding: c.1182C>T
MANE Select: NM_004168
dbSNP: rs377317558
Type: single nucleotide variant
Location: chr5:235261 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 5 PDB

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

Disease context

mitochondrial complex II deficiency, nuclear type 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma/paraganglioma syndrome 5 hereditary neoplastic syndrome

For Isolated succinate-CoQ reductase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SDHA p.Asp394Ala Uncertain significance ★ ⚠ same residue
SDHA p.Asp394Asn Uncertain significance ★ ⚠ same residue
SDHA p.Asp394Glu Uncertain significance ★ ⚠ same residue
SDHA c.1064+1G>A Likely pathogenic ★★ same condition
SDHA c.1064+1G>T Likely pathogenic ★★ same condition
SDHA c.1064+2T>A Likely pathogenic ★★ same condition
SDHA c.1065-2A>G Likely pathogenic ★★ same condition
SDHA c.1260+1G>T Likely pathogenic ★★ 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/sdha-p-asp394 (accessed [today's date]).

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