Is SDHB p.Ter281= (c.842_843insGC) pathogenic?

SDHB p.Ter281= (c.842843insGC) is classified Benign in SDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-13). Associated with pheochromocytoma/paraganglioma syndrome 4.

What condition is associated with SDHB p.Ter281= (c.842_843insGC)?

SDHB p.Ter281= (c.842_843insGC) is associated with pheochromocytoma/paraganglioma syndrome 4 (ClinVar).

SDHB p.Ter281=

c.842_843insGC · VCV3904598

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

Conditions

pheochromocytoma/paraganglioma syndrome 4

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function in a haploinsufficient gene (ClinGen)
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.063	GERP -5.6

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

Variant & gene context

Gene: SDHB
Protein: p.Ter281=
Coding: c.842_843insGC
MANE Select: NM_003000
Type: Insertion
Location: chr1:17018881 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB

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

Disease context

pheochromocytoma/paraganglioma syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SDHB p.Ter281Glu Uncertain significance ★★ same residue
SDHB p.Ala15delinsHisSerProTer Pathogenic ★★ same condition
SDHB p.Ala15fs Pathogenic ★★ same condition
SDHB p.Glu229fs Pathogenic ★ same condition
SDHB p.Ter281LeuextTer? Uncertain significance ★ same residue
SDHB c.424-14_424-13insCTC Likely benign ★ same condition
SDHB c.200+1G>A Pathogenic ★★ same condition
SDHB c.200+1G>C 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/sdhb-p-ter281 (accessed [today's date]).

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