Is CAD p.Arg2187fs (c.6558_6559dup) pathogenic?

CAD p.Arg2187fs (c.65586559dup) is classified Uncertain significance in CAD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-02-15). Absent from gnomAD.

How common is CAD p.Arg2187fs (c.6558_6559dup) in the general population?

CAD p.Arg2187fs (c.6558_6559dup) is absent from gnomAD (gnomAD).

CAD p.Arg2187fs

c.6558_6559dup · rs2148101657 · VCV1480917

Uncertain significance Single submitter

Classification

Uncertain significance

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	escapes	premature termination codon within the last 50 nt of the penultimate exon (43 of 44, 20 nt from its 3' end) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 2.3, 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.Arg2187fs
Coding: c.6558_6559dup
MANE Select: NM_004341
dbSNP: rs2148101657
Type: Duplication
Location: chr2:27243272 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 2187: a UniProt-annotated variant site (in dee50; uncertain significance); the 'atcase (aspartate transcarbamylase)' region

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

Similar variants

CAD p.Arg2187His Uncertain significance ★ ⚠ same residue
CAD p.Arg2187= Likely benign ★ same residue
CAD p.Gln1913fs Pathogenic/Likely pathogenic ★★ same type
CAD p.Ala1990fs Pathogenic ★ same type
CAD p.Asn570Ter Likely pathogenic ★ same type
CAD p.Asp1808fs Pathogenic ★ same type
CAD p.Cys2016fs Pathogenic ★ same type
CAD p.Gln1172fs 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-arg2187fs (accessed [today's date]).

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