Is SDHB p.Ile153= (c.459T>C) pathogenic?

SDHB p.Ile153= (c.459T>C) is classified Conflicting classifications of pathogenicity in SDHB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-03-23). Very rare (popmax 0.00133%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with SDHB p.Ile153= (c.459T>C)?

SDHB p.Ile153= (c.459T>C) is associated with hereditary neoplastic syndrome, pheochromocytoma/paraganglioma syndrome 4, pheochromocytoma (ClinVar).

How common is SDHB p.Ile153= (c.459T>C) in the general population?

SDHB p.Ile153= (c.459T>C) is very rare (popmax 0.00133%, afr) (gnomAD).

SDHB p.Ile153=

c.459T>C · rs2525017847 · VCV2932870

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5	GERP -4.1
Overall
CADD	1.132	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/75,022 alleles

Overall 0.000137% 2/1,460,632 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00133%	75,022
European (non-Finnish)	8.48e-05%	1,178,962

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.Ile153=
Coding: c.459T>C
MANE Select: NM_003000
dbSNP: rs2525017847
Type: single nucleotide variant
Location: chr1:17027830 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 153: the 'interaction with sdhaf1' region

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma/paraganglioma syndrome 4 pheochromocytoma gastrointestinal stromal tumor hereditary pheochromocytoma-paraganglioma

Similar variants

SDHB p.Ile153Thr Uncertain significance ★★ ⚠ same residue
SDHB p.Ile153Val Uncertain significance ★★ ⚠ same residue
SDHB p.Ile153Phe Uncertain significance ★ ⚠ same residue
SDHB p.Ile153_Glu154insTer 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
SDHB c.201-1G>C 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-ile153 (accessed [today's date]).

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