Is CAD p.Ala1272Val (c.3815C>T) pathogenic?

CAD p.Ala1272Val (c.3815C>T) is classified Uncertain significance in CAD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-06). AlphaMissense: likely benign (0.1584); Very rare (popmax 0.00332%, sas).

How common is CAD p.Ala1272Val (c.3815C>T) in the general population?

CAD p.Ala1272Val (c.3815C>T) is very rare (popmax 0.00332%, sas) (gnomAD).

What do computational predictors say about CAD p.Ala1272Val (c.3815C>T)?

AlphaMissense predicts likely benign (score 0.1584) — an in-silico prediction, not a clinical call.

CAD p.Ala1272Val

c.3815C>T · VCV3365113

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1584 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00332%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1584	likely benign
REVEL	0.738	pathogenic-leaning
SaProt	LLR -5.96	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 7.7	GERP 2, 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

Grpmax group 0.00332% South Asian · 3/90,466 alleles

Filtering AF 0.00103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000831%

Overall 0.00155% 25/1,610,910 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00332%	30,155
East Asian	0.00223%	44,802
European (non-Finnish)	0.00161%	62,034
Remaining individualsnot grpmax-eligible	0.0016%	62,338
Finnishnot grpmax-eligible	0.00156%	63,978

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.Ala1272Val
Coding: c.3815C>T
MANE Select: NM_004341
Type: single nucleotide variant
Location: chr2:27235273 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB
Residue 1272: the 'cpsase b' region; the 'cpsase (carbamoyl phosphate synthase)' region

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

Similar variants

CAD p.Ala1272= Uncertain significance ★ same residue
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

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-ala1272val (accessed [today's date]).

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