Is CDSN p.Ser353= (c.1059C>T) pathogenic?

CDSN p.Ser353= (c.1059C>T) is classified Benign in CDSN (ClinVar, Single submitter, 2 submitters; last evaluated 2026-02-04). Common (popmax 5.33%, sas) — too common for a highly-penetrant pathogenic allele.

CDSN p.Ser353=

Q: How common is CDSN p.Ser353= (c.1059C>T) in the general population?

CDSN p.Ser353= (c.1059C>T) is common (popmax 5.33%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1059C>T · rs36097319 · VCV790729

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.33%, sas) — 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 5	phastCons 1
Overall
CADD	11.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.33% South Asian · 4,852/91,066 alleles

Filtering AF 5.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.15%

Overall 0.419% 6,768/1,613,924 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	5.33%	19
African / African-American	0.894%	112
Remaining individualsnot grpmax-eligible	0.637%	157
East Asian	0.586%	171
Middle Eastern	0.445%	225
Admixed American	0.282%	355
Ashkenazi Jewishnot grpmax-eligible	0.0473%	2,115
European (non-Finnish)	0.0313%	3,198
Finnishnot grpmax-eligible	0.00783%	12,777

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: CDSN
Protein: p.Ser353=
Coding: c.1059C>T
MANE Select: NM_001264
dbSNP: rs36097319
Type: single nucleotide variant
Location: chr6:31116556 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 38.13

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

Similar variants

CDSN p.Lys59Ter Pathogenic ★★ same type
CDSN p.Cys423Ser Uncertain significance ★★ same type
CDSN p.Gly335Ala Uncertain significance ★★ same type
CDSN p.Pro226Ser Uncertain significance ★★ same type
CDSN p.Pro282Thr Uncertain significance ★★ same type
CDSN p.Pro447Leu Uncertain significance ★★ same type
CDSN p.Pro471Leu Uncertain significance ★★ same type
CDSN p.Ser159Gly 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/cdsn-p-ser353 (accessed [today's date]).

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