Is CADPS p.Ser1332Arg (c.3994A>C) pathogenic?

CADPS p.Ser1332Arg (c.3994A>C) is classified Uncertain significance in CADPS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-13). AlphaMissense: ambiguous (0.4647); Absent from gnomAD v4.1.

How common is CADPS p.Ser1332Arg (c.3994A>C) in the general population?

CADPS p.Ser1332Arg (c.3994A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CADPS p.Ser1332Arg (c.3994A>C)?

AlphaMissense predicts ambiguous (score 0.4647) — an in-silico prediction, not a clinical call.

CADPS p.Ser1332Arg

c.3994A>C · VCV3994704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4647 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4647	ambiguous
REVEL	0.056	moderately benign-leaning
SaProt	LLR -6.42	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.2	GERP 2.8, phastCons 1
Regional constraint	o/e 0.74	unconstrained · MANE · 75 kb · p 2.7e-05 · regional, not allelic
Overall
CADD	22.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CADPS
Protein: p.Ser1332Arg
Coding: c.3994A>C
MANE Select: NM_003716
Type: single nucleotide variant
Location: chr3:62399474 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 1 PDB
Residue 1332: the 'mediates targeting and association with dcvs' region; the 'disordered' region

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

Similar variants

CADPS p.Ser203= Benign ★★ same type
CADPS p.Tyr579= Benign ★★ same type
CAPS p.Arg18His Benign ★★ ⚠ same type
CAPS p.Pro88Thr Benign ★★ ⚠ same type
CADPS c.3477+2T>G Uncertain significance ★ same type
CADPS p.Ala1047Thr Uncertain significance ★ ⚠ same type
CADPS p.Ala1057Val Uncertain significance ★ ⚠ same type
CADPS p.Ala1114Thr 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/cadps-p-ser1332arg (accessed [today's date]).

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