Is CLDN25 p.Val53Asp (c.158T>A) pathogenic?

CLDN25 p.Val53Asp (c.158T>A) is classified Uncertain significance in CLDN25 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-06). AlphaMissense: likely benign (0.2851); Absent from gnomAD v4.1.

How common is CLDN25 p.Val53Asp (c.158T>A) in the general population?

CLDN25 p.Val53Asp (c.158T>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLDN25 p.Val53Asp (c.158T>A)?

AlphaMissense predicts likely benign (score 0.2851) — an in-silico prediction, not a clinical call.

CLDN25 p.Val53Asp

c.158T>A · VCV4003424

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2851 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2851	likely benign
REVEL	0.522	indeterminate
SaProt	LLR -8.88	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 686 bp · p 0.7 · regional, not allelic
Overall
CADD	18.05	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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: CLDN25
Protein: p.Val53Asp
Coding: c.158T>A
MANE Select: NM_001101389
Type: single nucleotide variant
Location: chr11:113779953 (GRCh38)
Gene constraint: LOEUF 1.892 · pLI 0.29 (gnomAD)
Structure: AlphaFold pLDDT 82.88

Full CLDN25 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLDN25 p.Ala143Ser Uncertain significance ★ ⚠ same type
CLDN25 p.Ala171Thr Uncertain significance ★ ⚠ same type
CLDN25 p.Ala61Asp Uncertain significance ★ ⚠ same type
CLDN25 p.Arg117Gln Uncertain significance ★ ⚠ same type
CLDN25 p.Arg117Trp Uncertain significance ★ ⚠ same type
CLDN25 p.Asn41Lys Uncertain significance ★ ⚠ same type
CLDN25 p.Asp147Asn Uncertain significance ★ ⚠ same type
CLDN25 p.Asp147His 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/cldn25-p-val53asp (accessed [today's date]).

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