Is CLDN16 p.Cys50= (c.150C>T) pathogenic?

CLDN16 p.Cys50= (c.150C>T) is classified Likely benign in CLDN16 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-19). Ultra-rare (popmax 0.016%, afr).

How common is CLDN16 p.Cys50= (c.150C>T) in the general population?

CLDN16 p.Cys50= (c.150C>T) is ultra-rare (popmax 0.016%, afr) (gnomAD).

CLDN16 p.Cys50=

c.150C>T · rs370592530 · VCV2162124

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.40 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.4	GERP -4.4
Overall
CADD	9.743	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.016% African / African-American · 12/74,882 alleles

Filtering AF 0.00922% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00722%

Overall 0.00248% 40/1,613,850 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0192%	5,207
African / African-Americangrpmax	0.016%	6,240
European (non-Finnish)	0.00127%	78,665
South Asian	0.0011%	91,078

Remaining individuals 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: CLDN16
Protein: p.Cys50=
Coding: c.150C>T
MANE Select: NM_006580
dbSNP: rs370592530
Type: single nucleotide variant
Location: chr3:190402372 (GRCh38)
Gene constraint: LOEUF 0.837 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.74
Residue 50: a UniProt-annotated variant site (in homg3; retained in the endoplasmic reticulum and targeted for proteasomal degradation)

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

Similar variants

CLDN16 p.Cys50Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
CLDN16 p.Cys50Tyr Conflicting classifications of pathogenicity ★ ⚠ same residue
CLDN16 c.217+1G>A Likely pathogenic ★★ same type
CLDN16 c.217+5G>A Pathogenic/Likely pathogenic ★★ same type
CLDN16 p.Arg146Cys Pathogenic/Likely pathogenic ★★ same type
CLDN16 p.Arg146His Pathogenic/Likely pathogenic ★★ ⚠ same type
CLDN16 p.Arg44Ter Pathogenic/Likely pathogenic ★★ same type
CLDN16 p.Arg79Ter Pathogenic ★★ 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/cldn16-p-cys50 (accessed [today's date]).

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