Is CADPS p.Ala912= (c.2736G>A) pathogenic?

CADPS p.Ala912= (c.2736G>A) is classified Likely benign in CADPS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-03-08). Ultra-rare (popmax 0.0318%, amr); Associated with CADPS-related disorder.

What condition is associated with CADPS p.Ala912= (c.2736G>A)?

CADPS p.Ala912= (c.2736G>A) is associated with CADPS-related disorder (ClinVar).

How common is CADPS p.Ala912= (c.2736G>A) in the general population?

CADPS p.Ala912= (c.2736G>A) is ultra-rare (popmax 0.0318%, amr) (gnomAD).

CADPS p.Ala912=

c.2736G>A · rs774402470 · VCV3051397

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0318%, amr)

Conditions

CADPS-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.072	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.9	GERP -4.2
Overall
CADD	7.898	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0318% Admixed American · 19/59,774 alleles

Filtering AF 0.0208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0172%

Overall 0.00298% 48/1,612,574 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0318%	3,146
African / African-American	0.00401%	24,950
Remaining individualsnot grpmax-eligible	0.0032%	31,207
European (non-Finnish)	0.00204%	49,135

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: CADPS
Protein: p.Ala912=
Coding: c.2736G>A
MANE Select: NM_003716
dbSNP: rs774402470
Type: single nucleotide variant
Location: chr3:62492438 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 1 PDB
Residue 912: the 'interaction with drd2' region

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

Disease context

CADPS-related disorder

Similar variants

CADPS c.3477+2T>G Uncertain significance ★ same condition
CADPS p.Ala564Val Uncertain significance ★ ⚠ same condition
CADPS p.Arg1198Ile Uncertain significance ★ ⚠ same condition
CADPS p.Gln1260= Uncertain significance ★ same condition
CADPS p.Gly1335Arg Uncertain significance ⚠ same condition
CADPS p.Leu1289Val Uncertain significance ⚠ same condition
CADPS c.1438-10T>C Likely benign same condition
CADPS c.1754-6T>C Likely benign 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/cadps-p-ala912 (accessed [today's date]).

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