Is SDHC p.Arg7= (c.19A>C) pathogenic?

SDHC p.Arg7= (c.19A>C) is classified Uncertain significance in SDHC (ClinVar, Single submitter, 1 submitter; last evaluated 2019-11-18). Absent from gnomAD v4.1; Associated with pheochromocytoma/paraganglioma syndrome 3.

What condition is associated with SDHC p.Arg7= (c.19A>C)?

SDHC p.Arg7= (c.19A>C) is associated with pheochromocytoma/paraganglioma syndrome 3, gastrointestinal stromal tumor (ClinVar).

How common is SDHC p.Arg7= (c.19A>C) in the general population?

SDHC p.Arg7= (c.19A>C) is absent from gnomAD v4.1 (gnomAD).

SDHC p.Arg7=

c.19A>C · rs1670521233 · VCV856348

Uncertain significance Single submitter

Classification

Uncertain significance

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/SpliceAI carries the signal.
REVEL	0.344	indeterminate
Splicing
SpliceAI	Δ0.73	donor loss · deltas
Pangolin	Δ0.49	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Overall
CADD	21.8	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.Arg7=
Coding: c.19A>C
MANE Select: NM_003001
dbSNP: rs1670521233
Type: single nucleotide variant
Location: chr1:161314424 (GRCh38)
Gene constraint: LOEUF 0.892 · pLI 0.05 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 91.05 · 2 PDB

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

Also linked: gastrointestinal stromal tumor

Similar variants

SDHC p.Arg7Lys Likely pathogenic ★★ ⚠ same residue
SDHC p.Arg7Gly Uncertain significance ★ ⚠ same residue
SDHC p.Arg7Ter Pathogenic/Likely 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
SDHC c.20+1G>T Likely pathogenic ★★ same condition
SDHC c.21-2A>G 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/sdhc-p-arg7 (accessed [today's date]).

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