Is SDHB p.Val140fs (c.418_419del) pathogenic?

SDHB p.Val140fs (c.418419del) is classified Pathogenic in SDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-16). Associated with pheochromocytoma.

What condition is associated with SDHB p.Val140fs (c.418_419del)?

SDHB p.Val140fs (c.418_419del) is associated with pheochromocytoma, pheochromocytoma/paraganglioma syndrome 4, gastrointestinal stromal tumor (ClinVar).

SDHB p.Val140fs

c.418_419del · VCV3757686

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 4 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.087	GERP -3.2, phastCons 0.018

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

Variant & gene context

Gene: SDHB
Protein: p.Val140fs
Coding: c.418_419del
MANE Select: NM_003000
Type: Deletion
Location: chr1:17028604 (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

Similar variants

SDHB p.Val140Phe Pathogenic/Likely pathogenic ★★ same residue
SDHB p.Val140Asp Conflicting classifications of pathogenicity ★ ⚠ 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
SDHB p.Gln30fs 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-val140fs (accessed [today's date]).

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