Is CLDN8 p.Ser201Phe (c.602C>T) pathogenic?

CLDN8 p.Ser201Phe (c.602C>T) is classified Uncertain significance in CLDN8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-08). AlphaMissense: likely benign (0.1289); Very rare (popmax 0.00678%, nfe).

How common is CLDN8 p.Ser201Phe (c.602C>T) in the general population?

CLDN8 p.Ser201Phe (c.602C>T) is very rare (popmax 0.00678%, nfe) (gnomAD).

What do computational predictors say about CLDN8 p.Ser201Phe (c.602C>T)?

AlphaMissense predicts likely benign (score 0.1289) — an in-silico prediction, not a clinical call.

CLDN8 p.Ser201Phe

c.602C>T · rs752677704 · VCV3145529

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1289 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00678%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1289	likely benign
REVEL	0.351	indeterminate
SaProt	LLR -11.39	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.2	GERP -0.015, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 674 bp · p 0.046 · regional, not allelic
Overall
CADD	21.2	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

Grpmax group 0.00678% European (non-Finnish) · 80/1,180,028 alleles

Filtering AF 0.00554% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.00539% 87/1,614,082 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00678%	14,750
Remaining individualsnot grpmax-eligible	0.0064%	15,622
Admixed American	0.00333%	30,003
Finnishnot grpmax-eligible	0.00156%	64,032

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: CLDN8
Protein: p.Ser201Phe
Coding: c.602C>T
MANE Select: NM_199328
dbSNP: rs752677704
Type: single nucleotide variant
Location: chr21:30215324 (GRCh38)
Gene constraint: LOEUF 1.865 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 79.71

Full CLDN8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLDN8 p.Ala94Val Benign ★★ same type
CLDN8 p.Met97Thr Benign ★★ same type
CLDN8 p.Ala180Val Uncertain significance ★ ⚠ same type
CLDN8 p.Ala86Thr Uncertain significance ★ ⚠ same type
CLDN8 p.Asp110Asn Uncertain significance ★ ⚠ same type
CLDN8 p.Glu112Lys Uncertain significance ★ ⚠ same type
CLDN8 p.Glu190Gly Uncertain significance ★ ⚠ same type
CLDN8 p.Gly101Ser 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/cldn8-p-ser201phe (accessed [today's date]).

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