Is CLDN16 p.Val119Phe (c.355G>T) pathogenic?

CLDN16 p.Val119Phe (c.355G>T) is classified Uncertain significance in CLDN16 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-30). AlphaMissense: likely benign (0.1184); Absent from gnomAD v4.1.

How common is CLDN16 p.Val119Phe (c.355G>T) in the general population?

CLDN16 p.Val119Phe (c.355G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLDN16 p.Val119Phe (c.355G>T)?

AlphaMissense predicts likely benign (score 0.1184) — an in-silico prediction, not a clinical call.

CLDN16 p.Val119Phe

c.355G>T · rs1719054513 · VCV837321

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1184 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1184	likely benign
REVEL	0.666	pathogenic-leaning
⇒ REVEL calls this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 1.6, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 22 kb · p 0.76 · regional, not allelic
Overall
CADD	22.1	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V189F vs ClinVar V119F) — verify the residue.

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: CLDN16
Protein: p.Val119Phe
Coding: c.355G>T
MANE Select: NM_006580
dbSNP: rs1719054513
Type: single nucleotide variant
Location: chr3:190404899 (GRCh38)
Gene constraint: LOEUF 0.837 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.74
Residue 119: a UniProt-annotated variant site (in homg3; retained in the endoplasmic reticulum and targeted for proteasomal degradation); a UniProt-annotated variant site (in homg3; retained intracellularly with predominant localization in the golgi apparatus and further targeted to lysosomes)

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

Similar variants

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
CLDN16 p.Asp35Asn Likely pathogenic ★★ same type
CLDN16 p.Gly128Asp Pathogenic/Likely 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-val119phe (accessed [today's date]).

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