Is SDHD p.Asp92fs (c.273_274dup) pathogenic?

SDHD p.Asp92fs (c.273274dup) is classified Pathogenic in SDHD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-19). No gnomAD frequency available for this variant; Associated with Carney-Stratakis syndrome.

What condition is associated with SDHD p.Asp92fs (c.273_274dup)?

SDHD p.Asp92fs (c.273_274dup) is associated with Carney-Stratakis syndrome, pheochromocytoma, Cowden syndrome 3 (ClinVar).

How common is SDHD p.Asp92fs (c.273_274dup) in the general population?

SDHD p.Asp92fs (c.273_274dup) 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.Asp92fs

c.273_274dup · rs2498905197 · VCV2949572

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (3 of 4, 42 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 5.1	GERP 2.1, phastCons 1

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.Asp92fs
Coding: c.273_274dup
MANE Select: NM_003002
dbSNP: rs2498905197
Type: Duplication
Location: chr11:112088969 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.50 · 2 PDB
Residue 92: a UniProt-annotated variant site (in mc2dn3; results in highly reduced protein expression; results in impaired cellular respiration); a UniProt-annotated variant site (in ppgl1); 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.Asp92Tyr Pathogenic/Likely pathogenic ★★ same residue
SDHD p.Asp92Val Likely pathogenic ★★ same residue
SDHD p.Asp92Glu Uncertain significance ★★ ⚠ same residue
SDHD p.Asp92Asn Uncertain significance ★ ⚠ same residue
SDHD p.Asp92= Likely benign ★ same residue
SDHD p.Ala130fs Pathogenic/Likely pathogenic ★★ same condition
SDHD p.Asp113Ter Pathogenic ★★ same condition
SDHD p.His50fs 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-asp92fs (accessed [today's date]).

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