Is CLDN16 p.Ile8= (c.24C>T) pathogenic?

CLDN16 p.Ile8= (c.24C>T) is classified Likely benign in CLDN16 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-10-19). Ultra-rare (popmax 0.0164%, mid); Associated with CLDN16-related disorder.

What condition is associated with CLDN16 p.Ile8= (c.24C>T)?

CLDN16 p.Ile8= (c.24C>T) is associated with CLDN16-related disorder (ClinVar).

How common is CLDN16 p.Ile8= (c.24C>T) in the general population?

CLDN16 p.Ile8= (c.24C>T) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

CLDN16 p.Ile8=

c.24C>T · rs372129081 · VCV3054655

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Conditions

CLDN16-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 -7	GERP -4.9
Overall
CADD	0.263	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0164% Middle Eastern · 1/6,082 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000805% 13/1,613,970 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,082
East Asian	0.00223%	44,872
Admixed American	0.00167%	59,994
European (non-Finnish)	0.000847%	118,001

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: CLDN16
Protein: p.Ile8=
Coding: c.24C>T
MANE Select: NM_006580
dbSNP: rs372129081
Type: single nucleotide variant
Location: chr3:190388353 (GRCh38)
Gene constraint: LOEUF 0.837 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.74

Full CLDN16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CLDN16-related disorder

Similar variants

CLDN16 p.Ile8Val Conflicting classifications of pathogenicity ★ ⚠ same residue
CLDN16 p.Arg146Cys Pathogenic/Likely pathogenic ★★ same condition
CLDN16 p.Leu81Phe Pathogenic ★★ ⚠ same condition
CLDN16 c.383-1G>C Likely pathogenic ★ same condition
CLDN16 c.-138C>T Likely pathogenic ★ same condition
CLDN16 p.Ser40Arg Pathogenic ★ same condition
CLDN16 p.Cys50Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
CLDN16 c.382+5C>T 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/cldn16-p-ile8 (accessed [today's date]).

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