Is CADPS p.Thr445= (c.1335C>T) pathogenic?

CADPS p.Thr445= (c.1335C>T) is classified Likely benign in CADPS (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-12-21). Rare (popmax 0.111%, nfe); Associated with CADPS-related disorder.

What condition is associated with CADPS p.Thr445= (c.1335C>T)?

CADPS p.Thr445= (c.1335C>T) is associated with CADPS-related disorder (ClinVar).

How common is CADPS p.Thr445= (c.1335C>T) in the general population?

CADPS p.Thr445= (c.1335C>T) is rare (popmax 0.111%, nfe) (gnomAD).

CADPS p.Thr445=

c.1335C>T · rs139420058 · VCV3035338

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.111%, nfe)

Conditions

CADPS-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP -2.3, phastCons 1
Overall
CADD	7.995	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.111% European (non-Finnish) · 1,311/1,179,552 alleles

Filtering AF 0.106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.104%

Overall 0.104% 1,677/1,613,542 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.306%	326
European (non-Finnish)grpmax	0.111%	900
South Asian	0.0966%	1,035
Remaining individualsnot grpmax-eligible	0.0688%	1,453
Admixed American	0.0333%	3,001
Middle Eastern	0.033%	3,031
Ashkenazi Jewishnot grpmax-eligible	0.027%	3,699
African / African-American	0.012%	8,336

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr445=
Coding: c.1335C>T
MANE Select: NM_003716
dbSNP: rs139420058
Type: single nucleotide variant
Location: chr3:62592739 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 1 PDB
Residue 445: the c2 domain

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-thr445 (accessed [today's date]).

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