Is SDHA c.1663+16del pathogenic?

SDHA c.1663+16del is classified Likely benign in SDHA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-19). Very rare (popmax 0.00134%, afr); Associated with mitochondrial complex II deficiency, nuclear type 1.

What condition is associated with SDHA c.1663+16del?

SDHA c.1663+16del is associated with mitochondrial complex II deficiency, nuclear type 1, pheochromocytoma/paraganglioma syndrome 5 (ClinVar).

How common is SDHA c.1663+16del in the general population?

SDHA c.1663+16del is very rare (popmax 0.00134%, afr) (gnomAD).

How is Isolated succinate-CoQ reductase deficiency inherited?

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

SDHA c.1663+16del

VCV3751071

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

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
Splice region	donor +16	near-intronic (+16 nt from the splice site)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.5	GERP -1.7
Non-coding constraint	Z 2.75	1 kb window · o/e 0.78 · regional · uncalibrated
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,882 alleles

Overall 6.22e-05% 1/1,608,462 alleles · very rare exomes 1/1,456,150 · genomes 0/152,312 · joint denominator

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
Coding: c.1663+16del
MANE Select: NM_004168
Type: Deletion
Location: chr5:251117 (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

For Isolated succinate-CoQ reductase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

SDHA c.1432_1432+1del Pathogenic/Likely pathogenic ★★ same condition
SDHA c.457-2_457del Pathogenic/Likely pathogenic ★★ same condition
SDHA c.63+2del Likely pathogenic ★★ same condition
SDHA c.762_770+17del Pathogenic/Likely pathogenic ★★ same condition
SDHA c.895+1del Likely pathogenic ★★ same condition
SDHA p.Ala338fs Pathogenic ★★ same condition
SDHA p.Ala582fs Pathogenic ★★ same condition
SDHA p.Arg162fs Pathogenic/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-c-1663-plus-16del (accessed [today's date]).

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