Is CADPS p.Ser203= (c.609C>T) pathogenic?

CADPS p.Ser203= (c.609C>T) is classified Benign in CADPS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-13). Common (popmax 5.48%, afr) — too common for a highly-penetrant pathogenic allele.

CADPS p.Ser203=

Q: How common is CADPS p.Ser203= (c.609C>T) in the general population?

CADPS p.Ser203= (c.609C>T) is common (popmax 5.48%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.609C>T · rs35975017 · VCV780383

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.48%, afr) — too common for a highly-penetrant pathogenic allele

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 -20	GERP -4.2
Overall
CADD	0.026	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.48% African / African-American · 4,108/75,018 alleles

Filtering AF 5.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.28%

Overall 0.299% 4,833/1,614,084 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.48%	18
Admixed American	0.457%	219
Remaining individualsnot grpmax-eligible	0.371%	269
Middle Eastern	0.264%	379
South Asian	0.0187%	5,357
European (non-Finnish)	0.0157%	6,378
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606

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.Ser203=
Coding: c.609C>T
MANE Select: NM_003716
dbSNP: rs35975017
Type: single nucleotide variant
Location: chr3:62753720 (GRCh38)
Gene constraint: LOEUF 0.445 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 1 PDB

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

Similar variants

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
CADPS p.Ala256Val 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-ser203 (accessed [today's date]).

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