Is SDHC p.Arg72= (c.216T>C) pathogenic?

SDHC p.Arg72= (c.216T>C) is classified Benign in SDHC (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-14). Absent from gnomAD v4.1; Associated with pheochromocytoma/paraganglioma syndrome 3.

What condition is associated with SDHC p.Arg72= (c.216T>C)?

SDHC p.Arg72= (c.216T>C) is associated with pheochromocytoma/paraganglioma syndrome 3 (ClinVar).

How common is SDHC p.Arg72= (c.216T>C) in the general population?

SDHC p.Arg72= (c.216T>C) is absent from gnomAD v4.1 (gnomAD).

SDHC p.Arg72=

c.216T>C · VCV3904413

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

pheochromocytoma/paraganglioma syndrome 3

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 -1.4	GERP -2.8
Overall
CADD	6.934	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: SDHC
Protein: p.Arg72=
Coding: c.216T>C
MANE Select: NM_003001
Type: single nucleotide variant
Location: chr1:161340630 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 91.05 · 2 PDB
Residue 72: an α-helix

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

Disease context

pheochromocytoma/paraganglioma syndrome 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

SDHC p.Arg72Cys Pathogenic/Likely pathogenic ★★ same residue
SDHC p.Arg72His Pathogenic/Likely pathogenic ★★ same residue
SDHC p.Arg72Gly Conflicting classifications of pathogenicity ★ ⚠ same residue
SDHC p.Arg72fs Pathogenic ★ same residue
SDHC p.Arg72Leu Pathogenic ★ same residue
SDHC c.179+1G>C Likely pathogenic ★★ same condition
SDHC c.179+1G>T Likely pathogenic ★★ same condition
SDHC c.180-2A>G 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/sdhc-p-arg72 (accessed [today's date]).

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