Is CDH19 p.Gln360Arg (c.1079A>G) pathogenic?

CDH19 p.Gln360Arg (c.1079A>G) is classified Likely benign in CDH19 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-02-07). AlphaMissense: likely benign (0.087); Rare (popmax 0.187%, amr); Associated with CDH19-related disorder.

What condition is associated with CDH19 p.Gln360Arg (c.1079A>G)?

CDH19 p.Gln360Arg (c.1079A>G) is associated with CDH19-related disorder (ClinVar).

How common is CDH19 p.Gln360Arg (c.1079A>G) in the general population?

CDH19 p.Gln360Arg (c.1079A>G) is rare (popmax 0.187%, amr) (gnomAD).

What do computational predictors say about CDH19 p.Gln360Arg (c.1079A>G)?

AlphaMissense predicts likely benign (score 0.087) — an in-silico prediction, not a clinical call.

CDH19 p.Gln360Arg

c.1079A>G · rs144091143 · VCV3034498

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.087 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.187%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CDH19-related disorder

Computational evidence

Protein change
AlphaMissense	0.087	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -7.32	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 0.63	GERP -5.5, phastCons 0.95
Regional constraint	o/e 1.11	unconstrained · MANE · 67 kb · p 0.00092 · regional, not allelic
Overall
CADD	12.87	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 0.187% Admixed American · 112/60,000 alleles

Filtering AF 0.159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.148%

Overall 0.00768% 124/1,613,918 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.187%	536
Remaining individualsnot grpmax-eligible	0.0128%	7,811
African / African-American	0.00133%	74,910
European (non-Finnish)	0.000254%	393,312

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.Gln360Arg
Coding: c.1079A>G
MANE Select: NM_021153
dbSNP: rs144091143
Type: single nucleotide variant
Location: chr18:66544106 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.14
Residue 360: the cadherin 3 domain

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

Disease context

CDH19-related disorder

Similar variants

CDH19 p.Gln360His Uncertain significance ★ ⚠ same residue
CDH19 p.Gly193= Uncertain significance ★ same condition
CDH19 p.Leu318Phe Uncertain significance ⚠ same condition
CDH19 c.1214+8T>C Likely benign same condition
CDH19 c.490+10A>G Likely benign same condition
CDH19 p.Ala653Asp Benign ⚠ same condition
CDH19 p.Ala712Thr Benign ⚠ same condition
CDH19 p.Asn25Asp Benign 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/cdh19-p-gln360arg (accessed [today's date]).

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