Is SDHD p.Ser52Ter (c.155C>A) pathogenic?

SDHD p.Ser52Ter (c.155C>A) is classified Pathogenic in SDHD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-14). No allele count reported in gnomAD v4.1 (AN 1,605,482); Associated with Carney-Stratakis syndrome.

What condition is associated with SDHD p.Ser52Ter (c.155C>A)?

SDHD p.Ser52Ter (c.155C>A) is associated with Carney-Stratakis syndrome, pheochromocytoma, Cowden syndrome 3 (ClinVar).

How common is SDHD p.Ser52Ter (c.155C>A) in the general population?

SDHD p.Ser52Ter (c.155C>A) is no allele count reported in gnomAD v4.1 (AN 1,605,482) (gnomAD).

How is Carney-Stratakis syndrome inherited?

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

SDHD p.Ser52Ter

c.155C>A · rs587782210 · VCV142068

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,605,482)

Conditions

Carney-Stratakis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 2 of 4
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.7	GERP 2.1, phastCons 1
Overall
CADD	37.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,605,482). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: SDHD
Protein: p.Ser52Ter
Coding: c.155C>A
MANE Select: NM_003002
dbSNP: rs587782210
Type: single nucleotide variant
Location: chr11:112087959 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.50 · 2 PDB

Full SDHD 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 Cowden syndrome 3 hereditary neoplastic syndrome

For Carney-Stratakis syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

SDHD p.Ser52Ala Uncertain significance ★ ⚠ same residue
SDHD p.Ser52Leu Uncertain significance ★ ⚠ same residue
SDHD c.170-1G>T Pathogenic ★★ same condition
SDHD c.170-2A>G Pathogenic/Likely pathogenic ★★ same condition
SDHD c.314+1G>A Pathogenic ★★ same condition
SDHD c.314+1G>T Pathogenic ★★ same condition
SDHD c.315-1G>A Likely pathogenic ★★ same condition
SDHD c.315-2A>C 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/sdhd-p-ser52ter (accessed [today's date]).

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