Is SDHB p.Pro141= (c.423C>T) pathogenic?

SDHB p.Pro141= (c.423C>T) is classified Likely benign in SDHB (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0147%, afr); Associated with gastrointestinal stromal tumor.

What condition is associated with SDHB p.Pro141= (c.423C>T)?

SDHB p.Pro141= (c.423C>T) is associated with gastrointestinal stromal tumor, pheochromocytoma/paraganglioma syndrome 4, pheochromocytoma (ClinVar).

How common is SDHB p.Pro141= (c.423C>T) in the general population?

SDHB p.Pro141= (c.423C>T) is ultra-rare (popmax 0.0147%, afr) (gnomAD).

How is Gastrointestinal stromal tumor inherited?

Typically Autosomal dominant, Not applicable (Orphanet). A genetic counselor can assess individual risk for a family.

SDHB p.Pro141=

c.423C>T · rs150542357 · VCV186513

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0147%, afr)

Conditions

gastrointestinal stromal tumor

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.52 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.8	GERP -4.4
Overall
CADD	9.229	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0147% African / African-American · 11/74,918 alleles

Filtering AF 0.00815% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00633%

Overall 0.00279% 45/1,613,948 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0147%	6,811
South Asian	0.00659%	15,180
Remaining individualsnot grpmax-eligible	0.0048%	20,826
East Asian	0.00223%	44,894
European (non-Finnish)	0.00203%	49,167

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SDHB
Protein: p.Pro141=
Coding: c.423C>T
MANE Select: NM_003000
dbSNP: rs150542357
Type: single nucleotide variant
Location: chr1:17028600 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB

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

Disease context

gastrointestinal stromal tumor — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma/paraganglioma syndrome 4 pheochromocytoma hereditary neoplastic syndrome hereditary pheochromocytoma-paraganglioma

For Gastrointestinal stromal tumor (Orphanet):

Inheritance: Autosomal dominant, Not applicable
Onset: Adolescent, Adult, Childhood
Prevalence: 1-5 / 10 000 (Europe)

Similar variants

SDHB p.Pro141Ala Uncertain significance ★ ⚠ same residue
SDHB p.Pro141Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHB p.Pro141Leu Uncertain significance ★ ⚠ 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
SDHB c.201-1G>C Pathogenic/Likely pathogenic ★★ same condition
SDHB c.201-2A>C 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-pro141 (accessed [today's date]).

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