Is CAD p.Leu2007Pro (c.6020T>C) pathogenic?

CAD p.Leu2007Pro (c.6020T>C) is classified Uncertain significance in CAD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-10-09). AlphaMissense: likely pathogenic (0.8033); Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with CAD p.Leu2007Pro (c.6020T>C)?

CAD p.Leu2007Pro (c.6020T>C) is associated with intellectual disability, epilepsy, developmental and epileptic encephalopathy, 50 (ClinVar).

How common is CAD p.Leu2007Pro (c.6020T>C) in the general population?

CAD p.Leu2007Pro (c.6020T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAD p.Leu2007Pro (c.6020T>C)?

AlphaMissense predicts likely pathogenic (score 0.8033) — an in-silico prediction, not a clinical call.

CAD p.Leu2007Pro

c.6020T>C · rs1676344855 · VCV830364

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.8033 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.8033	likely pathogenic
REVEL	0.984	strongly pathogenic-leaning
SaProt	LLR -15.23	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 2, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 2,068 bp · p 1.4e-06 · regional, not allelic
Overall
CADD	29.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CAD
Protein: p.Leu2007Pro
Coding: c.6020T>C
MANE Select: NM_004341
dbSNP: rs1676344855
Type: single nucleotide variant
Location: chr2:27242047 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 2007: a UniProt-annotated variant site (in dee50; uncertain significance); the 'atcase (aspartate transcarbamylase)' region; an α-helix

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epilepsy developmental and epileptic encephalopathy, 50

Similar variants

CAD p.Leu2007= Likely benign ★ same residue
CAD p.Arg1789Ter Pathogenic ★★ same condition
CAD p.Arg1810Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
CAD p.Arg191Ter Pathogenic ★★ same condition
CAD p.Gln1604Ter Likely pathogenic ★★ same condition
CAD p.Met33Arg Pathogenic ★★ same condition
CAD c.4315-3C>T Uncertain significance ★★ same condition
CAD c.996-13A>G Uncertain significance ★★ same condition

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-leu2007pro (accessed [today's date]).

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