Is CAD p.Arg1507Trp (c.4519C>T) pathogenic?

CAD p.Arg1507Trp (c.4519C>T) is classified Uncertain significance in CAD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-26). AlphaMissense: likely benign (0.1006); Very rare (popmax 0.00223%, eas); Associated with Inborn genetic diseases.

What condition is associated with CAD p.Arg1507Trp (c.4519C>T)?

CAD p.Arg1507Trp (c.4519C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CAD p.Arg1507Trp (c.4519C>T) in the general population?

CAD p.Arg1507Trp (c.4519C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CAD p.Arg1507Trp (c.4519C>T)?

AlphaMissense predicts likely benign (score 0.1006) — an in-silico prediction, not a clinical call.

CAD p.Arg1507Trp

c.4519C>T · rs149558703 · VCV2064612

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1006 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1006	likely benign
REVEL	0.163	moderately benign-leaning
SaProt	LLR -11.06	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP -0.23, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 2,919 bp · p 0.1 · regional, not allelic
Overall
CADD	26.3	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

Grpmax group 0.00223% East Asian · 1/44,900 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000744% 12/1,613,986 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,900
Admixed American	0.00167%	60,014
European (non-Finnish)	0.000847%	118,000

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.Arg1507Trp
Coding: c.4519C>T
MANE Select: NM_004341
dbSNP: rs149558703
Type: single nucleotide variant
Location: chr2:27237501 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 1507: the 'dhoase (dihydroorotase)' region; a β-strand

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.Arg1507Gln Uncertain significance ★ ⚠ same residue
CAD p.Arg1507= 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

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-arg1507trp (accessed [today's date]).

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