Is SDHB p.Cys68Arg (c.202T>C) pathogenic?

SDHB p.Cys68Arg (c.202T>C) is classified Conflicting classifications of pathogenicity in SDHB (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-05-12). AlphaMissense: likely pathogenic (0.9793); Absent from gnomAD v4.1; Associated with pheochromocytoma.

What condition is associated with SDHB p.Cys68Arg (c.202T>C)?

SDHB p.Cys68Arg (c.202T>C) is associated with pheochromocytoma, pheochromocytoma/paraganglioma syndrome 4, gastrointestinal stromal tumor (ClinVar).

How common is SDHB p.Cys68Arg (c.202T>C) in the general population?

SDHB p.Cys68Arg (c.202T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about SDHB p.Cys68Arg (c.202T>C)?

AlphaMissense predicts likely pathogenic (score 0.9793) — an in-silico prediction, not a clinical call.

SDHB p.Cys68Arg

c.202T>C · rs2101529119 · VCV1362008

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9793 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

pheochromocytoma

Computational evidence

Protein change
AlphaMissense	0.9793	likely pathogenic
REVEL	0.87	moderately pathogenic-leaning
SaProt	LLR -16.94	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.34 · evaluated, not missing
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 35 kb · p 0.67 · regional, not allelic
Overall
CADD	31.0	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.Cys68Arg
Coding: c.202T>C
MANE Select: NM_003000
dbSNP: rs2101529119
Type: single nucleotide variant
Location: chr1:17033144 (GRCh38)
Gene constraint: LOEUF 0.741 · pLI 0.03 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 92.14 · 6 PDB
Residue 68: 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

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

Also linked: pheochromocytoma/paraganglioma syndrome 4 gastrointestinal stromal tumor hereditary neoplastic syndrome

Similar variants

SDHB p.Cys68Tyr Pathogenic/Likely pathogenic ★★ same residue
SDHB p.Cys68= Benign/Likely benign ★★ same residue
SDHB p.Cys68Phe Likely pathogenic ★ same residue
SDHB p.Cys68Ser 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-cys68arg (accessed [today's date]).

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