Is CAD p.Ile1760Val (c.5278A>G) pathogenic?

CAD p.Ile1760Val (c.5278A>G) is classified Conflicting classifications of pathogenicity in CAD (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-01-29). AlphaMissense: likely benign (0.0772); Very rare (popmax 0.000254%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CAD p.Ile1760Val (c.5278A>G)?

CAD p.Ile1760Val (c.5278A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CAD p.Ile1760Val (c.5278A>G) in the general population?

CAD p.Ile1760Val (c.5278A>G) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about CAD p.Ile1760Val (c.5278A>G)?

AlphaMissense predicts likely benign (score 0.0772) — an in-silico prediction, not a clinical call.

CAD p.Ile1760Val

c.5278A>G · rs1399594906 · VCV1353572

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0772 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0772	likely benign
REVEL	0.279	benign-leaning
SaProt	LLR -4.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.35	GERP -4.1, phastCons 0.001
Regional constraint	o/e 0.93	unconstrained · MANE · 2,919 bp · p 0.1 · regional, not allelic
Overall
CADD	3.048	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 0.000254% European (non-Finnish) · 3/1,179,922 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000186% 3/1,613,804 alleles · very rare

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.Ile1760Val
Coding: c.5278A>G
MANE Select: NM_004341
dbSNP: rs1399594906
Type: single nucleotide variant
Location: chr2:27239355 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 1760: the 'dhoase (dihydroorotase)' 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 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
CAD p.Arg1181Gln 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-ile1760val (accessed [today's date]).

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