Is CAD p.Arg809Gln (c.2426G>A) pathogenic?

CAD p.Arg809Gln (c.2426G>A) is classified Uncertain significance in CAD (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-11). AlphaMissense: likely pathogenic (0.8736); Absent from gnomAD v4.1.

How common is CAD p.Arg809Gln (c.2426G>A) in the general population?

CAD p.Arg809Gln (c.2426G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CAD p.Arg809Gln (c.2426G>A)?

AlphaMissense predicts likely pathogenic (score 0.8736) — an in-silico prediction, not a clinical call.

CAD p.Arg809Gln

c.2426G>A · rs2465324876 · VCV2004698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8736 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8736	likely pathogenic
REVEL	0.933	strongly pathogenic-leaning
SaProt	LLR -12.70	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.2, phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 7,481 bp · p 8.7e-11 · regional, not allelic
Overall
CADD	33.0	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.Arg809Gln
Coding: c.2426G>A
MANE Select: NM_004341
dbSNP: rs2465324876
Type: single nucleotide variant
Location: chr2:27232005 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 809: 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.Arg1789Ter Pathogenic ★★ same type
CAD p.Arg1810Gln Pathogenic/Likely pathogenic ★★ ⚠ same type
CAD p.Arg191Ter Pathogenic ★★ same type
CAD p.Gln1604Ter Likely pathogenic ★★ same type
CAD p.Met33Arg Pathogenic ★★ same type
CAD c.1254+6G>A Uncertain significance ★★ same type
CAD c.2032-3C>T Uncertain significance ★★ same type
CAD c.2156+5G>A 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-arg809gln (accessed [today's date]).

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