Is SDHB p.Ser198fs (c.591del) pathogenic?

SDHB p.Ser198fs (c.591del) is classified Pathogenic in SDHB (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-06-18). Absent from gnomAD; Associated with pheochromocytoma/paraganglioma syndrome 4.

What condition is associated with SDHB p.Ser198fs (c.591del)?

SDHB p.Ser198fs (c.591del) is associated with pheochromocytoma/paraganglioma syndrome 4, pheochromocytoma, gastrointestinal stromal tumor (ClinVar).

How common is SDHB p.Ser198fs (c.591del) in the general population?

SDHB p.Ser198fs (c.591del) is absent from gnomAD (gnomAD).

SDHB p.Ser198fs

c.591del · rs1060503757 · VCV412462

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

pheochromocytoma/paraganglioma syndrome 4

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 6 of 8
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, 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.Ser198fs
Coding: c.591del
MANE Select: NM_003000
dbSNP: rs1060503757
Type: Deletion
Location: chr1:17024024 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 198: the 4fe-4s ferredoxin-type domain; the 'interaction with sdhaf1' region; an α-helix

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

Also linked: pheochromocytoma gastrointestinal stromal tumor hereditary neoplastic syndrome

Similar variants

SDHB p.Ser198Thr Uncertain significance ★★ ⚠ same residue
SDHB p.Ser198Ile 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
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-ser198fs (accessed [today's date]).

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