Is SDHD p.Ser68fs (c.204_205del) pathogenic?

SDHD p.Ser68fs (c.204205del) is classified Pathogenic in SDHD (ClinVar, Single submitter, 1 submitter; last evaluated 2019-09-27). No gnomAD frequency available for this variant; Associated with Carney-Stratakis syndrome.

What condition is associated with SDHD p.Ser68fs (c.204_205del)?

SDHD p.Ser68fs (c.204_205del) is associated with Carney-Stratakis syndrome, pheochromocytoma, Cowden syndrome 3 (ClinVar).

How common is SDHD p.Ser68fs (c.204_205del) in the general population?

SDHD p.Ser68fs (c.204_205del) is no gnomAD frequency available for this variant (gnomAD).

How is Carney-Stratakis syndrome inherited?

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

SDHD p.Ser68fs

c.204_205del · rs1865686266 · VCV942473

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Carney-Stratakis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 3 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.4	GERP -4.3, phastCons 0.97

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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.Ser68fs
Coding: c.204_205del
MANE Select: NM_003002
dbSNP: rs1865686266
Type: Deletion
Location: chr11:112088900 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.50 · 2 PDB
Residue 68: an α-helix

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

For Carney-Stratakis syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

SDHD p.Ser68= Benign/Likely benign ★★ same residue
SDHD p.Ser68Arg Uncertain significance ★ ⚠ same residue
SDHD p.Ser68Thr Uncertain significance ★ ⚠ same residue
SDHD p.Gln109fs Pathogenic ★★ same condition
SDHD p.Gly58fs Pathogenic ★★ same condition
SDHD p.Leu128fs Pathogenic ★★ same condition
SDHD p.Leu20fs Pathogenic ★★ same condition
SDHD p.Pro81fs 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-ser68fs (accessed [today's date]).

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