Is SDHB p.Ser152Pro (c.454T>C) pathogenic?

SDHB p.Ser152Pro (c.454T>C) is classified Uncertain significance in SDHB (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). AlphaMissense: likely pathogenic (0.9839); Very rare (popmax 6.2e-05%); Associated with hereditary pheochromocytoma-paraganglioma.

What condition is associated with SDHB p.Ser152Pro (c.454T>C)?

SDHB p.Ser152Pro (c.454T>C) is associated with hereditary pheochromocytoma-paraganglioma, Carney-Stratakis syndrome (ClinVar).

How common is SDHB p.Ser152Pro (c.454T>C) in the general population?

SDHB p.Ser152Pro (c.454T>C) is very rare (popmax 6.2e-05%) (gnomAD).

How is Hereditary pheochromocytoma-paraganglioma inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about SDHB p.Ser152Pro (c.454T>C)?

AlphaMissense predicts likely pathogenic (score 0.9839) — an in-silico prediction, not a clinical call.

SDHB p.Ser152Pro

c.454T>C · rs886045584 · VCV293810

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9839 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.2e-05%)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hereditary pheochromocytoma-paraganglioma

Computational evidence

Protein change
AlphaMissense	0.9839	likely pathogenic
REVEL	0.845	moderately pathogenic-leaning
SaProt	LLR -16.81	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 9.4	GERP 0.98, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 35 kb · p 0.67 · regional, not allelic
Overall
CADD	26.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.2e-05%

Overall 6.2e-05% 1/1,612,158 alleles · very rare exomes 1/1,460,018 · genomes 0/152,140 · 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.Ser152Pro
Coding: c.454T>C
MANE Select: NM_003000
dbSNP: rs886045584
Type: single nucleotide variant
Location: chr1:17027835 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 152: the 'interaction with sdhaf1' region; an α-helix

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

Disease context

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

Also linked: Carney-Stratakis syndrome

For Hereditary pheochromocytoma-paraganglioma (Orphanet):

Inheritance: Autosomal dominant
Onset: Childhood
Prevalence: 1-9 / 1 000 000 (Worldwide)

Similar variants

SDHB p.Ser152Phe Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHB p.Ser152= Benign/Likely benign ★★ same residue
SDHB p.Ser152Tyr Uncertain significance ★ ⚠ same residue
SDHB c.286+1G>A Pathogenic ★★ same condition
SDHB c.286+2T>A Pathogenic ★★ same condition
SDHB c.287-1G>C Pathogenic/Likely pathogenic ★★ same condition
SDHB c.287-3C>G Pathogenic/Likely pathogenic ★★ same condition
SDHB c.423+1G>A 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-ser152pro (accessed [today's date]).

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