Is SDHB p.Ser8= (c.24C>T) pathogenic?

SDHB p.Ser8= (c.24C>T) is classified Benign/Likely benign in SDHB (ClinVar, Multiple submitters, 23 submitters; last evaluated 2026-07-01). Rare (popmax 0.646%, nfe); Associated with hereditary neoplastic syndrome.

What condition is associated with SDHB p.Ser8= (c.24C>T)?

SDHB p.Ser8= (c.24C>T) is associated with hereditary neoplastic syndrome, pheochromocytoma/paraganglioma syndrome 4, pheochromocytoma (ClinVar).

How common is SDHB p.Ser8= (c.24C>T) in the general population?

SDHB p.Ser8= (c.24C>T) is rare (popmax 0.646%, nfe) (gnomAD).

SDHB p.Ser8=

c.24C>T · rs148738139 · VCV184192

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 23 submitters

gnomAD v4.1

Rare

rare (popmax 0.646%, nfe)

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 11	GERP 0.35, phastCons 1
Overall
CADD	14.91	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.646% European (non-Finnish) · 7,623/1,179,536 alleles

Filtering AF 0.634% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.629%

Overall 0.554% 8,934/1,612,708 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.43%	70
European (non-Finnish)grpmax	0.646%	155
Remaining individualsnot grpmax-eligible	0.382%	262
Amishnot grpmax-eligible	0.33%	303
Ashkenazi Jewishnot grpmax-eligible	0.193%	519
African / African-American	0.088%	1,137
Admixed American	0.0584%	1,713
South Asian	0.0033%	30,293

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser8=
Coding: c.24C>T
MANE Select: NM_003000
dbSNP: rs148738139
Type: single nucleotide variant
Location: chr1:17053996 (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

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

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

Similar variants

SDHB p.Ser8Cys Uncertain significance ★★ ⚠ same residue
SDHB p.Ser8Phe Uncertain significance ★★ ⚠ same residue
SDHB p.Ser8Pro Uncertain significance ★★ ⚠ same residue
SDHB p.Ser8Tyr Uncertain significance ★★ ⚠ same residue
SDHB p.Ser8Thr Uncertain significance ★ ⚠ same residue
SDHB p.Ser8fs 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-ser8 (accessed [today's date]).

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