Is CAD p.Ala1024Ser (c.3070G>T) pathogenic?

CAD p.Ala1024Ser (c.3070G>T) is classified Uncertain significance in CAD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-12). AlphaMissense: likely benign (0.282); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with CAD p.Ala1024Ser (c.3070G>T)?

CAD p.Ala1024Ser (c.3070G>T) is associated with Inborn genetic diseases (ClinVar).

How common is CAD p.Ala1024Ser (c.3070G>T) in the general population?

CAD p.Ala1024Ser (c.3070G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAD p.Ala1024Ser (c.3070G>T)?

AlphaMissense predicts likely benign (score 0.282) — an in-silico prediction, not a clinical call.

CAD p.Ala1024Ser

c.3070G>T · VCV3484255

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.282 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.282	likely benign
REVEL	0.845	moderately pathogenic-leaning
SaProt	LLR -8.56	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.50	unconstrained · MANE · 3,478 bp · p 1.8e-34 · regional, not allelic
Overall
CADD	27.9	PHRED · no single calibrated threshold — expert panels disagree

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.Ala1024Ser
Coding: c.3070G>T
MANE Select: NM_004341
Type: single nucleotide variant
Location: chr2:27233390 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 1024: the 'cpsase b' region; the 'cpsase (carbamoyl phosphate synthase)' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CAD p.Ala1024= Likely benign ★ same residue
CAD c.6480+6T>C Uncertain significance ★★ same condition
CAD p.Ala1527Thr Uncertain significance ★★ ⚠ same condition
CAD p.Ala1769Thr Uncertain significance ★★ ⚠ same condition
CAD p.Ala1824Ser Uncertain significance ★★ ⚠ same condition
CAD p.Ala495Pro Uncertain significance ★★ ⚠ same condition
CAD p.Ala608Thr Uncertain significance ★★ ⚠ same condition
CAD p.Arg1075His 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-ala1024ser (accessed [today's date]).

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