Is CAD p.Ala1990fs (c.5968dup) pathogenic?

CAD p.Ala1990fs (c.5968dup) is classified Pathogenic in CAD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-13). Absent from gnomAD.

How common is CAD p.Ala1990fs (c.5968dup) in the general population?

CAD p.Ala1990fs (c.5968dup) is absent from gnomAD (gnomAD).

CAD p.Ala1990fs

c.5968dup · rs2465367028 · VCV2843071

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 39 of 44
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -8.8	GERP -4.1

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.Ala1990fs
Coding: c.5968dup
MANE Select: NM_004341
dbSNP: rs2465367028
Type: Duplication
Location: chr2:27241994 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 1990: a UniProt-annotated variant site (in dee50; uncertain significance); the 'atcase (aspartate transcarbamylase)' region; a β-strand

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

Similar variants

CAD p.Ala1990Ser Uncertain significance ★ ⚠ same residue
CAD p.Gln1913fs Pathogenic/Likely 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
CAD p.Leu473fs Pathogenic ★ same type
CAD p.Phe1051fs 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-ala1990fs (accessed [today's date]).

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