Is SDHA p.Asp241= (c.723C>T) pathogenic?

SDHA p.Asp241= (c.723C>T) is classified Conflicting classifications of pathogenicity in SDHA (ClinVar, Conflicting submitters, 18 submitters; last evaluated 2026-05-01). Ultra-rare (popmax 0.0926%, nfe); Associated with mitochondrial complex II deficiency, nuclear type 1.

What condition is associated with SDHA p.Asp241= (c.723C>T)?

SDHA p.Asp241= (c.723C>T) is associated with mitochondrial complex II deficiency, nuclear type 1, Leigh syndrome, dilated cardiomyopathy 1GG (ClinVar).

How common is SDHA p.Asp241= (c.723C>T) in the general population?

SDHA p.Asp241= (c.723C>T) is ultra-rare (popmax 0.0926%, nfe) (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.Asp241=

c.723C>T · rs146653693 · VCV353203

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 18 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0926%, nfe)

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 -5.4	GERP -3.4
Overall
CADD	5.274	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0926% European (non-Finnish) · 1,093/1,179,822 alleles

Filtering AF 0.088% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0862%

Overall 0.0744% 1,201/1,613,656 alleles · ultra-rare exomes 1,133/1,461,616 · genomes 68/152,040 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.145%	688
European (non-Finnish)grpmax	0.0926%	1,079
Remaining individualsnot grpmax-eligible	0.0464%	2,154
Admixed American	0.035%	2,857
Finnishnot grpmax-eligible	0.0141%	7,109
African / African-American	0.00801%	12,477

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp241=
Coding: c.723C>T
MANE Select: NM_004168
dbSNP: rs146653693
Type: single nucleotide variant
Location: chr5:228286 (GRCh38)
Gene constraint: LOEUF 0.786 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.06 · 5 PDB
Residue 241: a turn

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: Leigh syndrome dilated cardiomyopathy 1GG pheochromocytoma/paraganglioma syndrome 5 hereditary neoplastic syndrome hereditary pheochromocytoma-paraganglioma neurodegeneration with ataxia and late-onset optic atrophy

For Isolated succinate-CoQ reductase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SDHA p.Asp241Asn Uncertain significance ★ ⚠ same residue
SDHA p.Asp241fs Pathogenic ★★ 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
SDHA c.1260+2T>A 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-asp241 (accessed [today's date]).

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