Is CLDN7 p.Pro151Ser (c.451C>T) pathogenic?

CLDN7 p.Pro151Ser (c.451C>T) is classified Uncertain significance in CLDN7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-07). AlphaMissense: ambiguous (0.4499); Very rare (popmax 0.00127%, nfe).

How common is CLDN7 p.Pro151Ser (c.451C>T) in the general population?

CLDN7 p.Pro151Ser (c.451C>T) is very rare (popmax 0.00127%, nfe) (gnomAD).

What do computational predictors say about CLDN7 p.Pro151Ser (c.451C>T)?

AlphaMissense predicts ambiguous (score 0.4499) — an in-silico prediction, not a clinical call.

CLDN7 p.Pro151Ser

c.451C>T · VCV3833862

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4499 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00127%, nfe)

Computational evidence

Protein change
AlphaMissense	0.4499	ambiguous
REVEL	0.529	indeterminate
SaProt	LLR -13.10	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.2	GERP -4.6
Regional constraint	o/e 1.08	unconstrained · MANE · 1,492 bp · p 0.27 · regional, not allelic
Overall
CADD	19.54	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 0.00127% European (non-Finnish) · 15/1,180,040 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.000991% 16/1,614,208 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)grpmax	0.00127%	78,670

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro151Ser
Coding: c.451C>T
MANE Select: NM_001307
Type: single nucleotide variant
Location: chr17:7260664 (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-pro151ser (accessed [today's date]).

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