Is CLDN6 p.Ala162Ser (c.484G>T) pathogenic?

CLDN6 p.Ala162Ser (c.484G>T) is classified Uncertain significance in CLDN6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-01). AlphaMissense: likely benign (0.1309); Very rare (popmax 8.48e-05%, nfe).

How common is CLDN6 p.Ala162Ser (c.484G>T) in the general population?

CLDN6 p.Ala162Ser (c.484G>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CLDN6 p.Ala162Ser (c.484G>T)?

AlphaMissense predicts likely benign (score 0.1309) — an in-silico prediction, not a clinical call.

CLDN6 p.Ala162Ser

c.484G>T · rs1296240804 · VCV2330381

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1309 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1309	likely benign
REVEL	0.267	benign-leaning
SaProt	LLR -9.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -1.8, phastCons 0.84
Regional constraint	o/e 0.98	unconstrained · MANE · 659 bp · p 0.76 · regional, not allelic
Overall
CADD	17.7	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,890 alleles

Overall 6.85e-05% 1/1,460,550 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CLDN6
Protein: p.Ala162Ser
Coding: c.484G>T
MANE Select: NM_021195
dbSNP: rs1296240804
Type: single nucleotide variant
Location: chr16:3015538 (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.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
CLDN6 p.Arg209Trp 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-ala162ser (accessed [today's date]).

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