Is CDSN p.Pro192Leu (c.575C>T) pathogenic?

CDSN p.Pro192Leu (c.575C>T) is classified Likely benign in CDSN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-09-15). Rare (popmax 0.281%, afr); Associated with Inborn genetic diseases.

What condition is associated with CDSN p.Pro192Leu (c.575C>T)?

CDSN p.Pro192Leu (c.575C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CDSN p.Pro192Leu (c.575C>T) in the general population?

CDSN p.Pro192Leu (c.575C>T) is rare (popmax 0.281%, afr) (gnomAD).

CDSN p.Pro192Leu

c.575C>T · rs150898829 · VCV2068522

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.281%, afr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.048	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	phastCons 0.52
Overall
CADD	4.702	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.281% African / African-American · 211/75,052 alleles

Filtering AF 0.25% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.238%

Overall 0.0256% 413/1,614,252 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.281%	356
Ashkenazi Jewishnot grpmax-eligible	0.0912%	1,097
Middle Eastern	0.066%	1,516
Admixed American	0.0516%	1,937
Remaining individualsnot grpmax-eligible	0.0368%	2,718
Finnishnot grpmax-eligible	0.0219%	4,575
European (non-Finnish)	0.00873%	11,457

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.Pro192Leu
Coding: c.575C>T
MANE Select: NM_001264
dbSNP: rs150898829
Type: single nucleotide variant
Location: chr6:31117040 (GRCh38)
Gene constraint: LOEUF 0.77 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 38.13
Residue 192: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDSN p.Cys423Ser Uncertain significance ★★ same condition
CDSN p.Gly335Ala Uncertain significance ★★ same condition
CDSN p.Pro226Ser Uncertain significance ★★ same condition
CDSN p.Pro471Leu Uncertain significance ★★ same condition
CDSN p.Ser159Gly Uncertain significance ★★ same condition
CDSN p.Ser274Asn Uncertain significance ★★ same condition
CDSN p.Val506Met Uncertain significance ★★ same condition
CDSN p.Ala368Gly Uncertain significance ★ 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/cdsn-p-pro192leu (accessed [today's date]).

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