Is CDH19 p.Tyr682Phe (c.2045A>T) pathogenic?

CDH19 p.Tyr682Phe (c.2045A>T) is classified Uncertain significance in CDH19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-02). AlphaMissense: likely benign (0.1227); Very rare (popmax 8.48e-05%, nfe).

How common is CDH19 p.Tyr682Phe (c.2045A>T) in the general population?

CDH19 p.Tyr682Phe (c.2045A>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about CDH19 p.Tyr682Phe (c.2045A>T)?

AlphaMissense predicts likely benign (score 0.1227) — an in-silico prediction, not a clinical call.

CDH19 p.Tyr682Phe

c.2045A>T · rs751703202 · VCV3141177

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1227 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1227	likely benign
REVEL	0.268	benign-leaning
SaProt	LLR -5.70	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 0.41	GERP -3.8, phastCons 0.003
Regional constraint	o/e 1.11	unconstrained · MANE · 67 kb · p 0.00092 · regional, not allelic
Overall
CADD	10.31	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 8.48e-05% European (non-Finnish) · 1/1,179,788 alleles

Overall 6.84e-05% 1/1,461,502 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: CDH19
Protein: p.Tyr682Phe
Coding: c.2045A>T
MANE Select: NM_021153
dbSNP: rs751703202
Type: single nucleotide variant
Location: chr18:66505086 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.14

Full CDH19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH19 p.Pro558= Benign ★★ same type
CDH19 p.Thr89Ile Benign ★★ same type
CDH7 c.1612+22C>T Benign ★★ same type
CDH7 c.1612+24A>T Benign ★★ same type
CDH7 c.1612+81T>C Benign ★★ same type
CDH7 c.1864+225A>G Benign ★★ same type
CDH7 c.210+52G>A Benign ★★ same type
CDH7 c.210+56T>G Benign ★★ 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/cdh19-p-tyr682phe (accessed [today's date]).

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