Is SDHB p.Val63= (c.189T>C) pathogenic?

SDHB p.Val63= (c.189T>C) is classified Likely benign in SDHB (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-05-15). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with SDHB p.Val63= (c.189T>C)?

SDHB p.Val63= (c.189T>C) is associated with hereditary neoplastic syndrome, pheochromocytoma/paraganglioma syndrome 4, pheochromocytoma (ClinVar).

How common is SDHB p.Val63= (c.189T>C) in the general population?

SDHB p.Val63= (c.189T>C) is absent from gnomAD v4.1 (gnomAD).

SDHB p.Val63=

c.189T>C · rs2101541333 · VCV1662632

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.24	GERP 0.89, phastCons 0.34
Overall
CADD	3.015	PHRED · no single calibrated threshold — expert panels disagree

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.Val63=
Coding: c.189T>C
MANE Select: NM_003000
dbSNP: rs2101541333
Type: single nucleotide variant
Location: chr1:17044772 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 63: the 2fe-2s ferredoxin-type domain; a β-strand

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

Similar variants

SDHB p.Val63Ala Uncertain significance ★★ ⚠ same residue
SDHB p.Val63Asp Uncertain significance ★ ⚠ same residue
SDHB p.Val63Ile Conflicting classifications of pathogenicity ★ ⚠ 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-val63 (accessed [today's date]).

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