SDHAF2

Chr 11

succinate dehydrogenase complex assembly factor 2

Also known as: C11orf79, PGL2, PPGL2, SDH5, hSDH5

NCBI Gene: 54949 ENSG00000167985 UniProt: Q9NX18

The protein is a mitochondrial assembly factor that enables flavination of the SDHA subunit, which is essential for succinate dehydrogenase complex activity. Mutations cause pheochromocytoma/paraganglioma syndrome 2, inherited in an autosomal dominant pattern. Loss of function mutations disrupt mitochondrial complex II assembly, leading to tumor formation in chromaffin tissue.

GeneReviews ResearchSummary from RefSeq, OMIM, UniProt

This gene encodes a mitochondrial assembly factor needed for the flavination of a succinate dehydrogenase complex subunit (SDHA), which is required for activity of the succinate dehydrogenase complex. Mutations in this gene are associated with paraganglioma. [provided by RefSeq, May 2022]

GeneReviews ResearchGenerating clinical summary…

Primary Disease Associations & Inheritance

UniProtPheochromocytoma/paraganglioma syndrome 2

Clinical highlights

Gene–disease validity (ClinGen)

Definitive · hereditary pheochromocytoma-paraganglioma · AD · ClinGen 2021

Active trials

Pubs (1 yr)

—

P/LP submissions

—

P/LP missense

1.81

LOEUF

LOF

Mechanism· predicted

📖

GeneReview available — SDHAF2

Authoritative clinical overview · Recommended first read

Open GeneReview ↗

Some data sources returned errors (1)

omim: Error: OMIM fetch failed: 429

Population Genetics & Constraint

gnomAD v4 — loss-of-function & missense intolerance

gnomAD

Tolerant — LoF & missense variants common in population

LoF Constraint?

1.81LOEUF

pLI 0.000

Z-score -0.28

OE 1.11 (0.65–1.81)

Tolerant

Highly tolerant — LoF variants common in population

Missense Constraint?

-0.14Z-score

OE missense 1.04 (0.88–1.24)

92 obs / 88.3 exp

Tolerant

Tolerant to missense variation

Observed / Expected Ratios?

LoF OE?1.11 (0.65–1.81)

0≤0.351.4

Missense OE?1.04 (0.88–1.24)

0≤0.61.4

Synonymous OE?1.17

0≤1.21.6

LoF obs/exp: 8 / 7.2Missense obs/exp: 92 / 88.3Syn Z: -0.75

Background carrier burden — how many people carry a rare variant somewhere in SDHAF2?

gnomAD v4 · ~731k individuals · PASS only

Rare means allele frequency under

Rare missense

1 in 250

254 rare PASS variants

Rare truncating (LoF)

1 in 2,700

56 rare PASS variants

Rare synonymous (reference)

1 in 620

92 rare PASS variants

Truncating variants are far rarer here than missense — that gap, in human units, is what constraint means for SDHAF2. A background rate for each class, not the frequency of any particular variant; thin-coverage exons undercount.

By genetic ancestry · 9 gnomAD groups · rare = under 0.1% in that group

Group	People	Missense	Truncating
European (non-Finnish)	~556k	1 in 330	1 in 3,400
South Asian	~43k	1 in 290	1 in 840
Remaining (unassigned)	~30k	1 in 190	1 in 3,000
European (Finnish)	~27k	1 in 950	none seen
Admixed American	~22k	1 in 350	≈ 1 in 7,500
African / African American	~21k	1 in 180	1 in 2,700
East Asian	~20k	1 in 340	≈ 1 in 9,900
Ashkenazi Jewish	~13k	1 in 570	none seen
Middle Eastern	~2,884	1 in 220	≈ 1 in 2,800

Each group is summed over the variants that are rare in that group. Grey ≈ figures rest on fewer than five expected carriers — too few to distinguish groups. Differences mostly reflect how many people were sampled and how much variation each ancestry carries, not disease risk.

Exome coverage (gnomAD): All 4 coding exons well covered in gnomAD exomes and genomes.? see exons ↓