Is SDHB p.Asp181= (c.543C>T) pathogenic?

SDHB p.Asp181= (c.543C>T) is classified Benign/Likely benign in SDHB (ClinVar, Multiple submitters, 9 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0133%, amr); Associated with Carney-Stratakis syndrome.

What condition is associated with SDHB p.Asp181= (c.543C>T)?

SDHB p.Asp181= (c.543C>T) is associated with Carney-Stratakis syndrome, pheochromocytoma/paraganglioma syndrome 4, pheochromocytoma (ClinVar).

How common is SDHB p.Asp181= (c.543C>T) in the general population?

SDHB p.Asp181= (c.543C>T) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

How is Carney-Stratakis syndrome inherited?

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

SDHB p.Asp181=

c.543C>T · rs199809975 · VCV417302

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 9 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Conditions

Carney-Stratakis syndrome

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 -7	GERP -4.1
Overall
CADD	1.402	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0133% Admixed American · 8/59,970 alleles

Filtering AF 0.00662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00542%

Overall 0.0064% 103/1,609,792 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,496
European (non-Finnish)	0.00714%	14,014
Remaining individualsnot grpmax-eligible	0.00641%	15,593
East Asian	0.00446%	22,439
South Asian	0.0033%	30,329
African / African-American	0.00267%	37,430

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: SDHB
Protein: p.Asp181=
Coding: c.543C>T
MANE Select: NM_003000
dbSNP: rs199809975
Type: single nucleotide variant
Location: chr1:17024072 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 181: the 4fe-4s ferredoxin-type domain; the 'interaction with sdhaf1' region; a turn

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

Disease context

Carney-Stratakis syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma/paraganglioma syndrome 4 pheochromocytoma gastrointestinal stromal tumor hereditary neoplastic syndrome hereditary pheochromocytoma-paraganglioma mitochondrial complex 2 deficiency, nuclear type 4

For Carney-Stratakis syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

SDHB p.Asp181Asn Uncertain significance ★★ ⚠ same residue
SDHB p.Asp181Glu Uncertain significance ★★ ⚠ same residue
SDHB p.Asp181Gly Uncertain significance ★★ ⚠ same residue
SDHB c.200+1G>A Pathogenic ★★ same condition
SDHB c.200+1G>C Pathogenic/Likely pathogenic ★★ same condition
SDHB c.200+5G>T Likely pathogenic ★★ same condition
SDHB c.201-1G>C Pathogenic/Likely pathogenic ★★ same condition
SDHB c.201-2A>C 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/sdhb-p-asp181 (accessed [today's date]).

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