Is SDHB p.Arg230fs (c.686_687dup) pathogenic?

SDHB p.Arg230fs (c.686687dup) is classified Pathogenic in SDHB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-19). Absent from gnomAD; Associated with pheochromocytoma.

What condition is associated with SDHB p.Arg230fs (c.686_687dup)?

SDHB p.Arg230fs (c.686_687dup) is associated with pheochromocytoma, pheochromocytoma/paraganglioma syndrome 4, gastrointestinal stromal tumor (ClinVar).

How common is SDHB p.Arg230fs (c.686_687dup) in the general population?

SDHB p.Arg230fs (c.686_687dup) is absent from gnomAD (gnomAD).

SDHB p.Arg230fs

c.686_687dup · rs2525004176 · VCV1755841

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 7 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1

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.Arg230fs
Coding: c.686_687dup
MANE Select: NM_003000
dbSNP: rs2525004176
Type: Duplication
Location: chr1:17022685 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 230: a UniProt-annotated variant site (in ppgl4); a UniProt-annotated variant site (in mc2dn4); a turn

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.Arg230Cys Pathogenic/Likely pathogenic ★★ same residue
SDHB p.Arg230His Pathogenic/Likely pathogenic ★★ same residue
SDHB p.Arg230Leu Pathogenic/Likely pathogenic ★★ same residue
SDHB p.Arg230= Benign/Likely benign ★★ same residue
SDHB p.Arg230Gly Likely pathogenic ★ same residue
SDHB p.Ala112fs Pathogenic ★★ same condition
SDHB p.Asn202fs Pathogenic/Likely pathogenic ★★ same condition
SDHB p.Asp204fs 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-arg230fs (accessed [today's date]).

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