Is SDHB p.Trp47Ter (c.141G>A) pathogenic?

SDHB p.Trp47Ter (c.141G>A) is classified Pathogenic in SDHB (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-02-06). Absent from gnomAD v4.1; Associated with pheochromocytoma/paraganglioma syndrome 4.

What condition is associated with SDHB p.Trp47Ter (c.141G>A)?

SDHB p.Trp47Ter (c.141G>A) is associated with pheochromocytoma/paraganglioma syndrome 4, pheochromocytoma, gastrointestinal stromal tumor (ClinVar).

How common is SDHB p.Trp47Ter (c.141G>A) in the general population?

SDHB p.Trp47Ter (c.141G>A) is absent from gnomAD v4.1 (gnomAD).

SDHB p.Trp47Ter

c.141G>A · rs1060503762 · VCV412474

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

pheochromocytoma/paraganglioma syndrome 4

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 2 of 8
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Overall
CADD	46.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

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.Trp47Ter
Coding: c.141G>A
MANE Select: NM_003000
dbSNP: rs1060503762
Type: single nucleotide variant
Location: chr1:17044820 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 47: the 2fe-2s ferredoxin-type domain

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.Trp47Arg Uncertain significance ★★ ⚠ same residue
SDHB p.Trp47Ser Uncertain significance ★★ ⚠ same residue
SDHB p.Trp47Cys Uncertain significance ★ ⚠ same residue
SDHB p.Trp47Gly Uncertain significance ★ ⚠ same residue
SDHB p.Trp47fs Pathogenic ★ same residue
SDHB c.200+1G>A Pathogenic ★★ same condition
SDHB c.200+1G>C Pathogenic/Likely pathogenic ★★ same condition
SDHB c.200+5G>T 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-trp47ter (accessed [today's date]).

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