Is CLDN7 p.Phe96Ser (c.287T>C) pathogenic?

CLDN7 p.Phe96Ser (c.287T>C) is classified Uncertain significance in CLDN7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-24). AlphaMissense: likely benign (0.2762); Very rare (popmax 0.000339%, nfe).

How common is CLDN7 p.Phe96Ser (c.287T>C) in the general population?

CLDN7 p.Phe96Ser (c.287T>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about CLDN7 p.Phe96Ser (c.287T>C)?

AlphaMissense predicts likely benign (score 0.2762) — an in-silico prediction, not a clinical call.

CLDN7 p.Phe96Ser

c.287T>C · VCV4654185

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2762 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2762	likely benign
REVEL	0.499	indeterminate
SaProt	LLR -6.10	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 6.2	GERP 0.23, phastCons 0.97
Regional constraint	o/e 1.08	unconstrained · MANE · 1,492 bp · p 0.27 · regional, not allelic
Overall
CADD	21.4	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 0.000339% European (non-Finnish) · 4/1,180,028 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,012 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: CLDN7
Protein: p.Phe96Ser
Coding: c.287T>C
MANE Select: NM_001307
Type: single nucleotide variant
Location: chr17:7260922 (GRCh38)
Gene constraint: LOEUF 1.198 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.45

Full CLDN7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLDN7 p.Ala133Pro Uncertain significance ★ ⚠ same type
CLDN7 p.Ala170Thr Uncertain significance ★ ⚠ same type
CLDN7 p.Ala180Thr Uncertain significance ★ ⚠ same type
CLDN7 p.Ala79Asp Uncertain significance ★ ⚠ same type
CLDN7 p.Arg106Leu Uncertain significance ★ ⚠ same type
CLDN7 p.Arg199Cys Uncertain significance ★ ⚠ same type
CLDN7 p.Arg199Gly Uncertain significance ★ ⚠ same type
CLDN7 p.Asn39Ile 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/cldn7-p-phe96ser (accessed [today's date]).

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