Is SDHB p.Lys255fs (c.764del) pathogenic?

SDHB p.Lys255fs (c.764del) is classified Pathogenic in SDHB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-23). Associated with pheochromocytoma.

What condition is associated with SDHB p.Lys255fs (c.764del)?

SDHB p.Lys255fs (c.764del) is associated with pheochromocytoma, pheochromocytoma/paraganglioma syndrome 4, gastrointestinal stromal tumor (ClinVar).

SDHB p.Lys255fs

c.764del · VCV4161253

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (7 of 8, 1 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 7.7	GERP 2, phastCons 1

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

Variant & gene context

Gene: SDHB
Protein: p.Lys255fs
Coding: c.764del
MANE Select: NM_003000
Type: Deletion
Location: chr1:17022609 (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 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma/paraganglioma syndrome 4 gastrointestinal stromal tumor hereditary neoplastic syndrome

Similar variants

SDHB p.Lys255Arg Uncertain significance ★★ ⚠ same residue
SDHB p.Lys255Asn Uncertain significance ★★ ⚠ same residue
SDHB p.Lys255Glu Uncertain significance ★★ ⚠ same residue
SDHB c.642_642+6del Pathogenic/Likely pathogenic ★★ same condition
SDHB p.Ala262fs Pathogenic/Likely pathogenic ★★ same condition
SDHB p.Asp138fs Pathogenic ★★ same condition
SDHB p.Asp161fs Pathogenic ★★ same condition
SDHB p.Gln164fs 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-lys255fs (accessed [today's date]).

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