Is SDHB p.Ser85fs (c.254_255del) pathogenic?

SDHB p.Ser85fs (c.254255del) is classified Pathogenic in SDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-08). Associated with pheochromocytoma.

What condition is associated with SDHB p.Ser85fs (c.254_255del)?

SDHB p.Ser85fs (c.254_255del) is associated with pheochromocytoma, pheochromocytoma/paraganglioma syndrome 4, gastrointestinal stromal tumor (ClinVar).

SDHB p.Ser85fs

c.254_255del · VCV4785502

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

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 3 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6.2	GERP 1.1, phastCons 1

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

Variant & gene context

Gene: SDHB
Protein: p.Ser85fs
Coding: c.254_255del
MANE Select: NM_003000
Type: Microsatellite
Location: chr1:17033091 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 85: the 2fe-2s ferredoxin-type domain

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.Ala190fs Pathogenic ★★ same condition
SDHB p.Leu111fs Pathogenic ★★ same condition
SDHB p.Ser239fs Pathogenic ★★ same condition
SDHB p.Thr227fs Pathogenic ★★ same condition
SDHB p.Lys160del Uncertain significance ★★ same condition
SDHB c.423+15CT[2] Likely benign ★★ same condition
SDHB c.424-37TTC[10] Benign/Likely benign ★★ same condition
SDHB c.424-37TTC[11] Benign/Likely benign ★★ 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-ser85fs (accessed [today's date]).

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