Is CDH19 p.Asp71Glu (c.213C>A) pathogenic?

CDH19 p.Asp71Glu (c.213C>A) is classified Uncertain significance in CDH19 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-25). AlphaMissense: ambiguous (0.5068); Ultra-rare (popmax 0.0844%, afr).

How common is CDH19 p.Asp71Glu (c.213C>A) in the general population?

CDH19 p.Asp71Glu (c.213C>A) is ultra-rare (popmax 0.0844%, afr) (gnomAD).

What do computational predictors say about CDH19 p.Asp71Glu (c.213C>A)?

AlphaMissense predicts ambiguous (score 0.5068) — an in-silico prediction, not a clinical call.

CDH19 p.Asp71Glu

c.213C>A · rs145183549 · VCV2399597

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5068 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0844%, afr)

Computational evidence

Protein change
AlphaMissense	0.5068	ambiguous
REVEL	0.305	indeterminate
SaProt	LLR -11.01	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP -2.8, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 67 kb · p 0.00092 · regional, not allelic
Overall
CADD	16.85	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 0.0844% African / African-American · 63/74,626 alleles

Filtering AF 0.0677% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0616%

Overall 0.00461% 74/1,605,060 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0844%	1,185
Remaining individualsnot grpmax-eligible	0.00965%	10,359
Admixed American	0.00675%	14,807
European (non-Finnish)	8.5e-05%	1,176,729

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.Asp71Glu
Coding: c.213C>A
MANE Select: NM_021153
dbSNP: rs145183549
Type: single nucleotide variant
Location: chr18:66568693 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.14
Residue 71: the cadherin 1 domain

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-asp71glu (accessed [today's date]).

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