Is SDHB p.Pro129= (c.387T>G) pathogenic?

SDHB p.Pro129= (c.387T>G) is classified Likely benign in SDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-30). Absent from gnomAD v4.1; Associated with hereditary pheochromocytoma-paraganglioma.

What condition is associated with SDHB p.Pro129= (c.387T>G)?

SDHB p.Pro129= (c.387T>G) is associated with hereditary pheochromocytoma-paraganglioma (ClinVar).

How common is SDHB p.Pro129= (c.387T>G) in the general population?

SDHB p.Pro129= (c.387T>G) is absent from gnomAD v4.1 (gnomAD).

How is Hereditary pheochromocytoma-paraganglioma inherited?

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

SDHB p.Pro129=

c.387T>G · VCV4757533

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary pheochromocytoma-paraganglioma

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	donor loss, 18 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.43	GERP -4.4
Overall
CADD	7.875	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: SDHB
Protein: p.Pro129=
Coding: c.387T>G
MANE Select: NM_003000
Type: single nucleotide variant
Location: chr1:17028636 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 129: the 2fe-2s ferredoxin-type domain

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.Pro129Ala Uncertain significance ★★ ⚠ same residue
SDHB p.Pro129Ser Uncertain significance ★★ ⚠ same residue
SDHB p.Pro129Arg Likely pathogenic ★ same residue
SDHB p.Pro129Thr 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

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-pro129 (accessed [today's date]).

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