Is SDHB p.Ile44= (c.132C>A) pathogenic?

SDHB p.Ile44= (c.132C>A) is classified Likely benign in SDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). Absent from gnomAD v4.1; Associated with pheochromocytoma.

What condition is associated with SDHB p.Ile44= (c.132C>A)?

SDHB p.Ile44= (c.132C>A) is associated with pheochromocytoma, pheochromocytoma/paraganglioma syndrome 4, gastrointestinal stromal tumor (ClinVar).

How common is SDHB p.Ile44= (c.132C>A) in the general population?

SDHB p.Ile44= (c.132C>A) is absent from gnomAD v4.1 (gnomAD).

SDHB p.Ile44=

c.132C>A · VCV3756596

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

pheochromocytoma

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 3.2	GERP -1.5, phastCons 1
Overall
CADD	9.992	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.Ile44=
Coding: c.132C>A
MANE Select: NM_003000
Type: single nucleotide variant
Location: chr1:17044829 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 44: 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

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

Also linked: pheochromocytoma/paraganglioma syndrome 4 gastrointestinal stromal tumor

Similar variants

SDHB p.Ile44Phe Uncertain significance ★★ ⚠ same residue
SDHB p.Ile44Val Uncertain significance ★★ ⚠ same residue
SDHB p.Ile44Met Uncertain significance ★ ⚠ same residue
SDHB p.Ile44Ser Uncertain significance ★ ⚠ same residue
SDHB p.Ile44Thr Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHB p.Ile44_Trp47delinsArg Likely pathogenic same residue
SDHB c.200+1G>A Pathogenic ★★ same condition
SDHB c.200+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-ile44 (accessed [today's date]).

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