Is CLDN5 p.Arg5Pro (c.14G>C) pathogenic?

CLDN5 p.Arg5Pro (c.14G>C) is classified Uncertain significance in CLDN5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-05). Absent from gnomAD v4.1.

How common is CLDN5 p.Arg5Pro (c.14G>C) in the general population?

CLDN5 p.Arg5Pro (c.14G>C) is absent from gnomAD v4.1 (gnomAD).

CLDN5 p.Arg5Pro

c.14G>C · VCV3901704

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.288	benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.53	GERP 1.4, phastCons 0.07
Overall
CADD	14.19	PHRED · no single calibrated threshold — expert panels disagree

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: CLDN5
Protein: p.Arg5Pro
Coding: c.14G>C
MANE Select: NM_001363066 · reported on NM_001130861
Type: single nucleotide variant
Location: chr22:19524497 (GRCh38)
Gene constraint: LOEUF 1.972 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.42

Full CLDN5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLDN5 p.Gly60Arg Pathogenic ★★ same type
CLDN5 p.Val41Met Pathogenic ★★ same type
CLDN5 c.*67G>T Benign ★★ same type
CLDN5 p.Gly101= Benign ★★ same type
CLDN5 p.Ser58Arg Likely pathogenic ★ same type
CLDN5 p.Thr59Ile Pathogenic ★ same type
CLDN5 c.-104G>T Uncertain significance ★ same type
CLDN5 c.-131C>A 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/cldn5-p-arg5pro (accessed [today's date]).

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