Is SDHA p.Ser50= (c.150C>T) pathogenic?

SDHA p.Ser50= (c.150C>T) is classified Likely benign in SDHA (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-10-01). Very rare (popmax 0.00401%, afr); Associated with pheochromocytoma/paraganglioma syndrome 5.

What condition is associated with SDHA p.Ser50= (c.150C>T)?

SDHA p.Ser50= (c.150C>T) is associated with pheochromocytoma/paraganglioma syndrome 5, hereditary neoplastic syndrome, mitochondrial complex II deficiency, nuclear type 1 (ClinVar).

How common is SDHA p.Ser50= (c.150C>T) in the general population?

SDHA p.Ser50= (c.150C>T) is very rare (popmax 0.00401%, afr) (gnomAD).

SDHA p.Ser50=

c.150C>T · rs140264486 · VCV472337

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00401%, afr)

Conditions

pheochromocytoma/paraganglioma syndrome 5

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 -4.1	GERP -3.7
Overall
CADD	1.055	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00401% African / African-American · 3/74,830 alleles

Filtering AF 0.00224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00199%

Overall 0.00267% 43/1,610,042 alleles · very rare exomes 40/1,457,902 · genomes 3/152,140 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00401%	24,943
European (non-Finnish)	0.00306%	32,678
East Asian	0.00223%	44,886
South Asian	0.0022%	45,502
Remaining individualsnot grpmax-eligible	0.0016%	62,352

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.Ser50=
Coding: c.150C>T
MANE Select: NM_004168
dbSNP: rs140264486
Type: single nucleotide variant
Location: chr5:223568 (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

pheochromocytoma/paraganglioma syndrome 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome mitochondrial complex II deficiency, nuclear type 1

Similar variants

SDHA p.Ser50Phe Uncertain significance ★★ ⚠ same residue
SDHA p.Ser50Tyr Uncertain significance ★★ ⚠ same residue
SDHA p.Ser50Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHA p.Ser50Cys 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

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-ser50 (accessed [today's date]).

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