Is CDH1 p.Pro3Thr (c.7C>A) pathogenic?

CDH1 p.Pro3Thr (c.7C>A) is classified Uncertain significance in CDH1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-09-26). AlphaMissense: likely benign (0.0644); Absent from gnomAD v4.1; Associated with ovarian cancer.

What condition is associated with CDH1 p.Pro3Thr (c.7C>A)?

CDH1 p.Pro3Thr (c.7C>A) is associated with ovarian cancer, hereditary neoplastic syndrome, hereditary breast carcinoma (ClinVar).

How common is CDH1 p.Pro3Thr (c.7C>A) in the general population?

CDH1 p.Pro3Thr (c.7C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH1 p.Pro3Thr (c.7C>A)?

AlphaMissense predicts likely benign (score 0.0644) — an in-silico prediction, not a clinical call.

CDH1 p.Pro3Thr

c.7C>A · rs1064793079 · VCV629094

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0644 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,534,102)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ovarian cancer

Computational evidence

Protein change
AlphaMissense	0.0644	likely benign
REVEL	0.039	moderately benign-leaning
SaProt	LLR -6.81	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 0.14	GERP -2.5, phastCons 0.17
Regional constraint	o/e 1.05	unconstrained · MANE · 71 kb · p 0.52 · regional, not allelic
Overall
CADD	8.204	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

No allele count reported in gnomAD v4.1 (AN 1,534,102). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CDH1
Protein: p.Pro3Thr
Coding: c.7C>A
MANE Select: NM_004360
dbSNP: rs1064793079
Type: single nucleotide variant
Location: chr16:68737422 (GRCh38)
Gene constraint: LOEUF 0.514 · pLI 0.86 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.13 · 22 PDB

Full CDH1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

ovarian cancer — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: hereditary neoplastic syndrome hereditary breast carcinoma

Similar variants

CDH1 p.Pro3Ser Uncertain significance ★★★ ⚠ same residue
CDH1 p.Pro3Arg Likely benign ★★★ same residue
CDH1 p.Pro3= Likely benign ★ same residue
CDH1 p.Pro3Phe Uncertain significance ★ same residue
CDH1 c.1008+2T>C Likely pathogenic ★★★ same condition
CDH1 c.1137+1G>A Pathogenic ★★★ same condition
CDH1 c.1137+2T>C Likely pathogenic ★★★ same condition
CDH1 c.1565+1G>A Pathogenic ★★★ same condition

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/cdh1-p-pro3thr (accessed [today's date]).

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