Is CDH15 p.Pro701His (c.2102C>A) pathogenic?

CDH15 p.Pro701His (c.2102C>A) is classified Uncertain significance in CDH15 (ClinVar, Single submitter, 1 submitter; last evaluated 2015-06-17). AlphaMissense: likely benign (0.0822); Absent from gnomAD v4.1.

How common is CDH15 p.Pro701His (c.2102C>A) in the general population?

CDH15 p.Pro701His (c.2102C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH15 p.Pro701His (c.2102C>A)?

AlphaMissense predicts likely benign (score 0.0822) — an in-silico prediction, not a clinical call.

CDH15 p.Pro701His

c.2102C>A · rs864309589 · VCV218658

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0822 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0822	likely benign
REVEL	0.115	moderately benign-leaning
SaProt	LLR -7.42	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 0.009	GERP -2.6
Regional constraint	o/e 1.18	unconstrained · MANE · 23 kb · p 5e-10 · regional, not allelic
Overall
CADD	11.91	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

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: CDH15
Protein: p.Pro701His
Coding: c.2102C>A
MANE Select: NM_004933
dbSNP: rs864309589
Type: single nucleotide variant
Location: chr16:89193864 (GRCh38)
Gene constraint: LOEUF 1.41 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 78.70
Residue 701: the 'disordered' region

Full CDH15 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH3 p.Tyr701= Likely benign ★★ same residue
CDH3 p.Tyr701His Uncertain significance ★ same residue
CDH3 c.1796-2A>G Pathogenic ★★ same type
CDH3 c.691+1G>A Pathogenic/Likely pathogenic ★★ same type
CDH3 p.Arg103Ter Pathogenic ★★ same type
CDH3 p.Arg221Ter Pathogenic ★★ same type
CDH3 p.Arg503His Pathogenic/Likely pathogenic ★★ ⚠ same type
CDH3 p.Gln299Ter Pathogenic ★★ 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/cdh15-p-pro701his (accessed [today's date]).

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