Is SDHD p.Arg17= (c.51A>C) pathogenic?

SDHD p.Arg17= (c.51A>C) is classified Conflicting classifications of pathogenicity in SDHD (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-01-31). Very rare (popmax 0.00446%, eas); Associated with Carney-Stratakis syndrome.

What condition is associated with SDHD p.Arg17= (c.51A>C)?

SDHD p.Arg17= (c.51A>C) is associated with Carney-Stratakis syndrome, pheochromocytoma, Cowden syndrome 3 (ClinVar).

How common is SDHD p.Arg17= (c.51A>C) in the general population?

SDHD p.Arg17= (c.51A>C) is very rare (popmax 0.00446%, eas) (gnomAD).

How is Carney-Stratakis syndrome inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

SDHD p.Arg17=

c.51A>C · rs199890548 · VCV239474

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Conditions

Carney-Stratakis syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.37	donor gain · deltas
Pangolin	Δ0.36	loss · gain 0.15 · SpliceAI calls gain · independent
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Overall
CADD	23.7	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00446% East Asian · 2/44,872 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000124% 2/1,614,030 alleles · very rare exomes 2/1,461,854 · genomes 0/152,176 · joint denominator

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: SDHD
Protein: p.Arg17=
Coding: c.51A>C
MANE Select: NM_003002
dbSNP: rs199890548
Type: single nucleotide variant
Location: chr11:112086958 (GRCh38)
Gene constraint: LOEUF 0.581 · pLI 0.91 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 81.50 · 2 PDB

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

Disease context

Carney-Stratakis syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: pheochromocytoma Cowden syndrome 3 hereditary neoplastic syndrome

For Carney-Stratakis syndrome (Orphanet):

Inheritance: Autosomal dominant
Onset: Adolescent, Adult

Similar variants

SDHD c.170-1G>T Pathogenic ★★ same condition
SDHD c.170-2A>G Pathogenic/Likely pathogenic ★★ same condition
SDHD c.314+1G>A Pathogenic ★★ same condition
SDHD c.314+1G>T Pathogenic ★★ same condition
SDHD c.315-1G>A Likely pathogenic ★★ same condition
SDHD c.315-2A>C Pathogenic/Likely pathogenic ★★ same condition
SDHD c.315-2A>T Pathogenic/Likely pathogenic ★★ same condition
SDHD p.Arg22Ter 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/sdhd-p-arg17 (accessed [today's date]).

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