Is SDHB p.Ala3= (c.9G>C) pathogenic?

SDHB p.Ala3= (c.9G>C) is classified Likely benign in SDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-19). Very rare (popmax 0.0011%, sas); Associated with pheochromocytoma.

What condition is associated with SDHB p.Ala3= (c.9G>C)?

SDHB p.Ala3= (c.9G>C) is associated with pheochromocytoma, pheochromocytoma/paraganglioma syndrome 4, gastrointestinal stromal tumor (ClinVar).

How common is SDHB p.Ala3= (c.9G>C) in the general population?

SDHB p.Ala3= (c.9G>C) is very rare (popmax 0.0011%, sas) (gnomAD).

SDHB p.Ala3=

c.9G>C · rs1350879010 · VCV1126928

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 -1.8	GERP -2.2
Overall
CADD	9.532	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/90,588 alleles

Overall 6.21e-05% 1/1,610,854 alleles · very rare exomes 1/1,458,486 · genomes 0/152,368 · joint denominator

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.Ala3=
Coding: c.9G>C
MANE Select: NM_003000
dbSNP: rs1350879010
Type: single nucleotide variant
Location: chr1:17054011 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 3: a UniProt-annotated variant site (found in a patient with a cowden-like phenotype; uncertain significance; patient cells have increased manganese superoxide dismutase expression and normal levels of reactive oxygen species; 1.2-fold increase in akt expression and 1.3-fold change in mapk expression in patient cells)

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.Ala3Thr Uncertain significance ★★ ⚠ same residue
SDHB p.Ala3Val Uncertain significance ★★ ⚠ same residue
SDHB p.Ala3Gly Benign/Likely benign ★★ same residue
SDHB p.Ala3Glu 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

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-ala3 (accessed [today's date]).

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