Is CLDN7 p.Ala79Asp (c.236C>A) pathogenic?

CLDN7 p.Ala79Asp (c.236C>A) is classified Uncertain significance in CLDN7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-09). AlphaMissense: likely pathogenic (0.9885); Absent from gnomAD v4.1.

How common is CLDN7 p.Ala79Asp (c.236C>A) in the general population?

CLDN7 p.Ala79Asp (c.236C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLDN7 p.Ala79Asp (c.236C>A)?

AlphaMissense predicts likely pathogenic (score 0.9885) — an in-silico prediction, not a clinical call.

CLDN7 p.Ala79Asp

c.236C>A · VCV4229615

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9885 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9885	likely pathogenic · top 10% in CLDN7
REVEL	0.934	strongly pathogenic-leaning
SaProt	LLR -15.55	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.3, phastCons 1
Regional constraint	o/e 1.08	unconstrained · MANE · 1,492 bp · p 0.27 · regional, not allelic
Overall
CADD	28.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: CLDN7
Protein: p.Ala79Asp
Coding: c.236C>A
MANE Select: NM_001307
Type: single nucleotide variant
Location: chr17:7260973 (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.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
CLDN7 p.Asn3Ser 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-ala79asp (accessed [today's date]).

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