Is CDSN p.Arg184Cys (c.550C>T) pathogenic?

CDSN p.Arg184Cys (c.550C>T) is classified Uncertain significance in CDSN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). Very rare (popmax 0.000678%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CDSN p.Arg184Cys (c.550C>T)?

CDSN p.Arg184Cys (c.550C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDSN p.Arg184Cys (c.550C>T) in the general population?

CDSN p.Arg184Cys (c.550C>T) is very rare (popmax 0.000678%, nfe) (gnomAD).

CDSN p.Arg184Cys

c.550C>T · rs748468507 · VCV2300993

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000678%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.056	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	phastCons 0.95
Overall
CADD	18.69	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000678% European (non-Finnish) · 8/1,180,056 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000558% 9/1,614,100 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
European (non-Finnish)grpmax	0.000678%	147,507

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CDSN
Protein: p.Arg184Cys
Coding: c.550C>T
MANE Select: NM_001264
dbSNP: rs748468507
Type: single nucleotide variant
Location: chr6:31117065 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 38.13
Residue 184: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDSN p.Cys423Ser Uncertain significance ★★ same condition
CDSN p.Gly335Ala Uncertain significance ★★ same condition
CDSN p.Pro226Ser Uncertain significance ★★ same condition
CDSN p.Pro471Leu Uncertain significance ★★ same condition
CDSN p.Ser159Gly Uncertain significance ★★ same condition
CDSN p.Ser274Asn Uncertain significance ★★ same condition
CDSN p.Val506Met Uncertain significance ★★ same condition
CDSN p.Pro192Leu Likely benign ★★ 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/cdsn-p-arg184cys (accessed [today's date]).

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