Is SDHB p.His132Pro (c.395A>C) pathogenic?

SDHB p.His132Pro (c.395A>C) is classified Pathogenic/Likely pathogenic in SDHB (ClinVar, Multiple submitters, 3 submitters; last evaluated 2021-10-24). AlphaMissense: likely pathogenic (0.9681); Absent from gnomAD v4.1; Associated with pheochromocytoma/paraganglioma syndrome 4.

What condition is associated with SDHB p.His132Pro (c.395A>C)?

SDHB p.His132Pro (c.395A>C) is associated with pheochromocytoma/paraganglioma syndrome 4, pheochromocytoma, gastrointestinal stromal tumor (ClinVar).

How common is SDHB p.His132Pro (c.395A>C) in the general population?

SDHB p.His132Pro (c.395A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SDHB p.His132Pro (c.395A>C)?

AlphaMissense predicts likely pathogenic (score 0.9681) — an in-silico prediction, not a clinical call.

SDHB p.His132Pro

c.395A>C · rs74315372 · VCV12787

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9681 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pheochromocytoma/paraganglioma syndrome 4

Computational evidence

Protein change
AlphaMissense	0.9681	likely pathogenic ✓ concordant with ClinVar
REVEL	0.96	strongly pathogenic-leaning
SaProt	LLR -15.57	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 35 kb · p 0.67 · regional, not allelic
Overall
CADD	27.5	PHRED · no single calibrated threshold — expert panels disagree

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

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.His132Pro
Coding: c.395A>C
MANE Select: NM_003000
dbSNP: rs74315372
Type: single nucleotide variant
Location: chr1:17028628 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 132: the 2fe-2s ferredoxin-type domain; a UniProt-annotated variant site (in ppgl4); a β-strand

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

Disease context

pheochromocytoma/paraganglioma syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma gastrointestinal stromal tumor hereditary neoplastic syndrome

Similar variants

SDHB p.His132Arg Uncertain significance ★★ ⚠ same residue
SDHB p.His132= Benign/Likely benign ★★ same residue
SDHB p.His132Gln Uncertain significance ★ same residue
SDHB p.His132Tyr 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-his132pro (accessed [today's date]).

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