Is SDHD p.Ala33fs (c.94_95del) pathogenic?

SDHD p.Ala33fs (c.9495del) is classified Pathogenic in SDHD (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-07-09). No gnomAD frequency available for this variant; Associated with pheochromocytoma/paraganglioma syndrome 1.

What condition is associated with SDHD p.Ala33fs (c.94_95del)?

SDHD p.Ala33fs (c.94_95del) is associated with pheochromocytoma/paraganglioma syndrome 1, pheochromocytoma, Carney-Stratakis syndrome (ClinVar).

How common is SDHD p.Ala33fs (c.94_95del) in the general population?

SDHD p.Ala33fs (c.94_95del) is no gnomAD frequency available for this variant (gnomAD).

SDHD p.Ala33fs

c.94_95del · rs397514034 · VCV6908

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

pheochromocytoma/paraganglioma syndrome 1

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 2 of 4
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.7	GERP -1.2, phastCons 0.99

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.Ala33fs
Coding: c.94_95del
MANE Select: NM_003002
dbSNP: rs397514034
Type: Microsatellite
Location: chr11:112087896 (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

pheochromocytoma/paraganglioma syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma Carney-Stratakis syndrome Cowden syndrome 3 hereditary neoplastic syndrome hereditary pheochromocytoma-paraganglioma mitochondrial complex 2 deficiency, nuclear type 3

Similar variants

SDHD p.Ala33= Likely benign ★★ same residue
SDHD p.Ala33Glu Uncertain significance ★ ⚠ same residue
SDHD p.Ala33Thr Uncertain significance ★ ⚠ same residue
SDHD p.Ile49fs Pathogenic ★★ same condition
SDHD p.Ala90fs Pathogenic ★ same condition
SDHD c.53-10_53-9del Uncertain significance ★ same condition
SDHD p.Ala33Val Uncertain significance ★ ⚠ same residue
SDHD p.Met1fs Uncertain significance ★ 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-ala33fs (accessed [today's date]).

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