Is CDSN p.Pro282Ser (c.844C>T) pathogenic?

CDSN p.Pro282Ser (c.844C>T) is classified Uncertain significance in CDSN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-10). Ultra-rare (popmax 0.0356%, eas); Associated with Inborn genetic diseases.

What condition is associated with CDSN p.Pro282Ser (c.844C>T)?

CDSN p.Pro282Ser (c.844C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDSN p.Pro282Ser (c.844C>T) in the general population?

CDSN p.Pro282Ser (c.844C>T) is ultra-rare (popmax 0.0356%, eas) (gnomAD).

CDSN p.Pro282Ser

c.844C>T · VCV3489775

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0356%, eas)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.174	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	phastCons 1
Overall
CADD	24.2	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0356% East Asian · 16/44,882 alleles

Filtering AF 0.0223% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0182%

Overall 0.00124% 20/1,613,226 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0356%	2,805
Remaining individualsnot grpmax-eligible	0.0016%	62,480
European (non-Finnish)	0.000254%	393,346

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.Pro282Ser
Coding: c.844C>T
MANE Select: NM_001264
Type: single nucleotide variant
Location: chr6:31116771 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 38.13

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.Pro282Thr Uncertain significance ★★ same residue
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

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-pro282ser (accessed [today's date]).

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