Is SDHB p.Val83Ter (c.243_246dup) pathogenic?

SDHB p.Val83Ter (c.243246dup) is classified Pathogenic in SDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-25). Absent from gnomAD; Associated with gastrointestinal stromal tumor.

What condition is associated with SDHB p.Val83Ter (c.243_246dup)?

SDHB p.Val83Ter (c.243_246dup) is associated with gastrointestinal stromal tumor, pheochromocytoma/paraganglioma syndrome 4, pheochromocytoma (ClinVar).

How common is SDHB p.Val83Ter (c.243_246dup) in the general population?

SDHB p.Val83Ter (c.243_246dup) is absent from gnomAD (gnomAD).

How is Gastrointestinal stromal tumor inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

SDHB p.Val83Ter

c.243_246dup · rs2101528972 · VCV1455849

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	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 0.038	GERP -3.5, phastCons 0.33

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.Val83Ter
Coding: c.243_246dup
MANE Select: NM_003000
dbSNP: rs2101528972
Type: Duplication
Location: chr1:17033099 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 83: the 2fe-2s ferredoxin-type domain

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

Disease context

gastrointestinal stromal tumor — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma/paraganglioma syndrome 4 pheochromocytoma

For Gastrointestinal stromal tumor (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

SDHB p.Val83Ala Uncertain significance ★ ⚠ same residue
SDHB p.Val83Gly Uncertain significance ★ ⚠ same residue
SDHB p.Val83Ile Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHB p.Val83= Likely benign ★ 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

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-val83ter (accessed [today's date]).

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