Is SDHB p.Val124fs (c.369_370insA) pathogenic?

SDHB p.Val124fs (c.369370insA) is classified Pathogenic in SDHB (ClinVar, No assertion criteria, 1 submitter). Absent from gnomAD; Associated with hereditary pheochromocytoma-paraganglioma.

What condition is associated with SDHB p.Val124fs (c.369_370insA)?

SDHB p.Val124fs (c.369_370insA) is associated with hereditary pheochromocytoma-paraganglioma (ClinVar).

How common is SDHB p.Val124fs (c.369_370insA) in the general population?

SDHB p.Val124fs (c.369_370insA) is absent from gnomAD (gnomAD).

How is Hereditary pheochromocytoma-paraganglioma inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

SDHB p.Val124fs

c.369_370insA · rs1553177742 · VCV438415

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

hereditary pheochromocytoma-paraganglioma

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 7.7	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.Val124fs
Coding: c.369_370insA
MANE Select: NM_003000
dbSNP: rs1553177742
Type: Insertion
Location: chr1:17028653 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 124: the 2fe-2s ferredoxin-type domain; a β-strand

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

Disease context

hereditary pheochromocytoma-paraganglioma — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Hereditary pheochromocytoma-paraganglioma (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

SDHB p.Val124Ala Uncertain significance ★ ⚠ same residue
SDHB p.Val124Ile Uncertain significance ★ ⚠ same residue
SDHB p.Val124Phe Uncertain significance ★ ⚠ same residue
SDHB c.286+1G>A Pathogenic ★★ same condition
SDHB c.286+2T>A Pathogenic ★★ same condition
SDHB c.287-1G>C Pathogenic/Likely pathogenic ★★ same condition
SDHB c.287-3C>G Pathogenic/Likely pathogenic ★★ same condition
SDHB c.423+1G>A 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-val124fs (accessed [today's date]).

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