Is CAD p.Cys1455fs (c.4364_4365del) pathogenic?

CAD p.Cys1455fs (c.43644365del) is classified Likely pathogenic in CAD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-01). Absent from gnomAD.

How common is CAD p.Cys1455fs (c.4364_4365del) in the general population?

CAD p.Cys1455fs (c.4364_4365del) is absent from gnomAD (gnomAD).

CAD p.Cys1455fs

c.4364_4365del · rs2465343084 · VCV2571067

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 27 of 44
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1	GERP -3.3, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CAD
Protein: p.Cys1455fs
Coding: c.4364_4365del
MANE Select: NM_004341
dbSNP: rs2465343084
Type: Deletion
Location: chr2:27236797 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 1455: the 'cpsase b' region; the mgs-like domain; the 'cpsase (carbamoyl phosphate synthase)' region

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

Similar variants

CAD p.Cys1455Arg Uncertain significance ★ ⚠ same residue
CAD p.Gly725fs Pathogenic/Likely pathogenic ★★ same type
CAD p.Phe1766fs Pathogenic ★★ same type
CAD c.2401-6_2401-3del Likely benign ★★ same type
CAD c.6576-5del Benign ★★ same type
CAD c.2031+2_2031+12del Likely pathogenic ★ same type
CAD c.3618+1del Likely pathogenic ★ same type
CAD c.6320_6378+11del Likely 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/cad-p-cys1455fs (accessed [today's date]).

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