Is SDHB p.Asp48= (c.144C>T) pathogenic?

SDHB p.Asp48= (c.144C>T) is classified Conflicting classifications of pathogenicity in SDHB (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-03-14). Very rare (popmax 0.00133%, afr); Associated with hereditary neoplastic syndrome.

What condition is associated with SDHB p.Asp48= (c.144C>T)?

SDHB p.Asp48= (c.144C>T) is associated with hereditary neoplastic syndrome, pheochromocytoma/paraganglioma syndrome 4, pheochromocytoma (ClinVar).

How common is SDHB p.Asp48= (c.144C>T) in the general population?

SDHB p.Asp48= (c.144C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

SDHB p.Asp48=

c.144C>T · rs1553178737 · VCV528757

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 1.4	GERP -3.2, phastCons 1
Overall
CADD	7.483	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,912 alleles

Overall 0.000657% 1/152,160 alleles · very rare

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.Asp48=
Coding: c.144C>T
MANE Select: NM_003000
dbSNP: rs1553178737
Type: single nucleotide variant
Location: chr1:17044817 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 48: the 2fe-2s ferredoxin-type domain; a UniProt-annotated variant site (in mc2dn4; decreased succinate dehydrogenase (ubiquinone) activity in homozygous patient cells; decreased protein levels in homozygous patient cells)

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.Asp48Asn Uncertain significance ★ ⚠ same residue
SDHB p.Asp48Val Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHB p.Asp48fs 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
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-asp48 (accessed [today's date]).

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