Is CLDN2 p.Asp65His (c.193G>C) pathogenic?

CLDN2 p.Asp65His (c.193G>C) is classified Uncertain significance in CLDN2 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.6291); Absent from gnomAD v4.1.

How common is CLDN2 p.Asp65His (c.193G>C) in the general population?

CLDN2 p.Asp65His (c.193G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLDN2 p.Asp65His (c.193G>C)?

AlphaMissense predicts likely pathogenic (score 0.6291) — an in-silico prediction, not a clinical call.

CLDN2 p.Asp65His

c.193G>C · rs387907423 · VCV64495

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6291 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6291	likely pathogenic
REVEL	0.675	pathogenic-leaning
SaProt	LLR -7.13	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 0.79, phastCons 1
Regional constraint	o/e 0.37	unconstrained · MANE · 284 bp · p 1e-07 · regional, not allelic
Overall
CADD	26.3	PHRED · no single calibrated threshold — expert panels disagree

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: CLDN2
Protein: p.Asp65His
Coding: c.193G>C
MANE Select: NM_020384
dbSNP: rs387907423
Type: single nucleotide variant
Location: chrX:106928421 (GRCh38)
Structure: AlphaFold pLDDT 78.99 · 1 PDB
Residue 65: a functional site (paracellular cation selectivity)

Full CLDN2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

RIPPLY1 p.Thr83= Benign ★★ same type
RIPPLY1 p.Tyr131= Benign ★★ same type
CLDN2 p.Ala89Thr Uncertain significance ★ ⚠ same type
CLDN2 p.Asp154Glu Uncertain significance ★ ⚠ same type
CLDN2 p.Gly10Ala Uncertain significance ★ ⚠ same type
CLDN2 p.Leu164Val Uncertain significance ★ ⚠ same type
CLDN2 p.Lys216Glu Uncertain significance ★ ⚠ same type
CLDN2 p.Pro209Thr 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/cldn2-p-asp65his (accessed [today's date]).

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