Is CLDN6 p.Trp47Arg (c.139T>A) pathogenic?

CLDN6 p.Trp47Arg (c.139T>A) is classified Uncertain significance in CLDN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). AlphaMissense: likely pathogenic (0.9695); Absent from gnomAD v4.1.

How common is CLDN6 p.Trp47Arg (c.139T>A) in the general population?

CLDN6 p.Trp47Arg (c.139T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLDN6 p.Trp47Arg (c.139T>A)?

AlphaMissense predicts likely pathogenic (score 0.9695) — an in-silico prediction, not a clinical call.

CLDN6 p.Trp47Arg

c.139T>A · VCV3493443

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9695 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9695	likely pathogenic · top 6% in CLDN6
REVEL	0.813	moderately pathogenic-leaning
SaProt	LLR -11.62	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 659 bp · p 0.76 · regional, not allelic
Overall
CADD	29.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CLDN6
Protein: p.Trp47Arg
Coding: c.139T>A
MANE Select: NM_021195
Type: single nucleotide variant
Location: chr16:3015883 (GRCh38)
Gene constraint: LOEUF 1.765 · pLI 0.24 (gnomAD)
Structure: AlphaFold pLDDT 80.36

Full CLDN6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLDN6 p.Thr14= Benign ★★ same type
CLDN6 p.Ala155Thr Uncertain significance ★ ⚠ same type
CLDN6 p.Ala162Ser Uncertain significance ★ ⚠ same type
CLDN6 p.Ala169Val Uncertain significance ★ ⚠ same type
CLDN6 p.Ala72Val Uncertain significance ★ ⚠ same type
CLDN6 p.Arg116Cys Uncertain significance ★ ⚠ same type
CLDN6 p.Arg199Cys Uncertain significance ★ ⚠ same type
CLDN6 p.Arg199His 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/cldn6-p-trp47arg (accessed [today's date]).

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