Is CAD p.Val722fs (c.2165_2166del) pathogenic?

CAD p.Val722fs (c.21652166del) is classified Pathogenic in CAD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). Very rare (popmax 6.84e-05%).

How common is CAD p.Val722fs (c.2165_2166del) in the general population?

CAD p.Val722fs (c.2165_2166del) is very rare (popmax 6.84e-05%) (gnomAD).

CAD p.Val722fs

c.2165_2166del · rs2465306996 · VCV3009230

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

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 15 of 44
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.7	GERP -4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,838 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: CAD
Protein: p.Val722fs
Coding: c.2165_2166del
MANE Select: NM_004341
dbSNP: rs2465306996
Type: Microsatellite
Location: chr2:27226838 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 722: the 'cpsase (carbamoyl phosphate synthase)' region; the 'cpsase a' region

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

Similar variants

CAD p.Val722= Likely benign ★ same residue
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.Arg1874fs Pathogenic ★ same type
CAD p.Phe312fs Pathogenic ★ same type
CAD p.Thr793fs Likely pathogenic ★ same type
CAD p.1516LA[3] Uncertain significance ★ 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-val722fs (accessed [today's date]).

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