Is CAD p.1516LA[3] (c.4547TGGCCC[3]) pathogenic?

CAD p.1516LA[3] (c.4547TGGCCC[3]) is classified Uncertain significance in CAD (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-17). Very rare (popmax 0.0011%, sas).

How common is CAD p.1516LA[3] (c.4547TGGCCC[3]) in the general population?

CAD p.1516LA[3] (c.4547TGGCCC[3]) is very rare (popmax 0.0011%, sas) (gnomAD).

CAD p.1516LA[3]

c.4547TGGCCC[3] · rs1326257429 · VCV1460583

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -2.6	GERP -4

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,042 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,238 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,042
European (non-Finnish)	0.00017%	589,936

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.1516LA[3]
Coding: c.4547TGGCCC[3]
MANE Select: NM_004341
dbSNP: rs1326257429
Type: Microsatellite
Location: chr2:27237527 (GRCh38)
Gene constraint: LOEUF 0.409 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 87.25 · 57 PDB

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

Similar variants

CAD p.Val357fs Likely pathogenic ★★ same type
CAD p.Glu1694del Uncertain significance ★★ same type
CAD c.2032-8_2032-6del Likely benign ★★ same type
CAD p.Arg1874fs Pathogenic ★ same type
CAD p.Phe312fs Pathogenic ★ same type
CAD p.Thr793fs Likely pathogenic ★ same type
CAD p.Val722fs Pathogenic ★ same type
CAD c.1109-14_1109-12del Likely benign ★ 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-1516la-3 (accessed [today's date]).

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