Is CAD p.Arg1874fs (c.5619_5620del) pathogenic?

CAD p.Arg1874fs (c.56195620del) is classified Pathogenic in CAD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-07). Absent from gnomAD.

How common is CAD p.Arg1874fs (c.5619_5620del) in the general population?

CAD p.Arg1874fs (c.5619_5620del) is absent from gnomAD (gnomAD).

CAD p.Arg1874fs

c.5619_5620del · rs1676285984 · VCV2766717

Pathogenic Single submitter

Classification

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 36 of 44
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.1	GERP 1, phastCons 0.006

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.Arg1874fs
Coding: c.5619_5620del
MANE Select: NM_004341
dbSNP: rs1676285984
Type: Microsatellite
Location: chr2:27240933 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 1874: a UniProt-annotated variant site (in dee50; uncertain significance); the 'linker' region; the 'disordered' region

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

Similar variants

CAD p.Val357fs Likely pathogenic ★★ same type
CAD p.Glu1694del Uncertain significance ★★ same type
CAD c.2032-8_2032-6del Likely benign ★★ same type
CAD p.Phe312fs Pathogenic ★ same type
CAD p.Thr793fs Likely pathogenic ★ same type
CAD p.Val722fs Pathogenic ★ same type
CAD p.1516LA[3] Uncertain significance ★ same type
CAD c.1109-14_1109-12del Likely benign ★ 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-arg1874fs (accessed [today's date]).

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