Is SDHB p.Asp48fs (c.84_141dup) pathogenic?

SDHB p.Asp48fs (c.84141dup) is classified Pathogenic in SDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-19). Absent from gnomAD; Associated with pheochromocytoma.

What condition is associated with SDHB p.Asp48fs (c.84_141dup)?

SDHB p.Asp48fs (c.84_141dup) is associated with pheochromocytoma, pheochromocytoma/paraganglioma syndrome 4, gastrointestinal stromal tumor (ClinVar).

How common is SDHB p.Asp48fs (c.84_141dup) in the general population?

SDHB p.Asp48fs (c.84_141dup) is absent from gnomAD (gnomAD).

SDHB p.Asp48fs

c.84_141dup · rs2525059744 · VCV2954035

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

pheochromocytoma

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 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 4.8	GERP 1.9, 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: SDHB
Protein: p.Asp48fs
Coding: c.84_141dup
MANE Select: NM_003000
dbSNP: rs2525059744
Type: Duplication
Location: chr1:17044819 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 48: the 2fe-2s ferredoxin-type domain; a UniProt-annotated variant site (in mc2dn4; decreased succinate dehydrogenase (ubiquinone) activity in homozygous patient cells; decreased protein levels in homozygous patient cells)

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

Disease context

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

Also linked: pheochromocytoma/paraganglioma syndrome 4 gastrointestinal stromal tumor

Similar variants

SDHB p.Asp48= Conflicting classifications of pathogenicity ★ same residue
SDHB p.Asp48Asn Uncertain significance ★ ⚠ same residue
SDHB p.Asp48Val Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHB p.Arg230fs Pathogenic ★★ same condition
SDHB p.Asn202fs Pathogenic/Likely pathogenic ★★ same condition
SDHB p.Asp204fs Pathogenic ★★ same condition
SDHB p.Ile263fs Likely pathogenic ★★ same condition
SDHB p.Leu180fs 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-asp48fs (accessed [today's date]).

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