Is CDSN p.Ser455fs (c.1364del) pathogenic?

CDSN p.Ser455fs (c.1364del) is classified Uncertain significance in CDSN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-28). Very rare (popmax 0.000847%, nfe).

How common is CDSN p.Ser455fs (c.1364del) in the general population?

CDSN p.Ser455fs (c.1364del) is very rare (popmax 0.000847%, nfe) (gnomAD).

CDSN p.Ser455fs

c.1364del · rs1772107812 · VCV1967420

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000847%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.94
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000847% European (non-Finnish) · 10/1,179,976 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.00062% 10/1,613,958 alleles · very rare

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.Ser455fs
Coding: c.1364del
MANE Select: NM_001264
dbSNP: rs1772107812
Type: Deletion
Location: chr6:31116251 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 38.13
Residue 455: the 'disordered' region

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

Similar variants

CDSN p.Ser195fs Likely pathogenic ★ same type
CDSN p.Asn527fs Uncertain significance ★ same type
PSORS1C1 c.-229+1133_-229+1145delinsATGGACTGTC Uncertain significance ★ same type
CDSN p.Ser153del Benign ★ same type
CDSN p.Gly249fs Pathogenic same type

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-ser455fs (accessed [today's date]).

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