Is CDH19 p.Val597= (c.1791C>T) pathogenic?

CDH19 p.Val597= (c.1791C>T) is classified Benign in CDH19 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-08). Common (popmax 16.3%, eas) — too common for a highly-penetrant pathogenic allele; Associated with CDH19-related disorder.

What condition is associated with CDH19 p.Val597= (c.1791C>T)?

CDH19 p.Val597= (c.1791C>T) is associated with CDH19-related disorder (ClinVar).

CDH19 p.Val597=

Q: How common is CDH19 p.Val597= (c.1791C>T) in the general population?

CDH19 p.Val597= (c.1791C>T) is common (popmax 16.3%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1791C>T · rs3764472 · VCV3059447

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 16.3%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

CDH19-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.41 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.29	GERP -1.8
Overall
CADD	0.706	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.3% East Asian · 7,321/44,784 alleles

Filtering AF 16% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.9%

Overall 1.65% 26,650/1,611,996 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	16.3%	6
Admixed American	7.6%	13
African / African-American	7%	14
South Asian	6.12%	16
Remaining individualsnot grpmax-eligible	2.28%	44
Middle Eastern	1.51%	66
Ashkenazi Jewishnot grpmax-eligible	1.17%	86
Finnishnot grpmax-eligible	0.916%	109
European (non-Finnish)	0.13%	766

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.Val597=
Coding: c.1791C>T
MANE Select: NM_021153
dbSNP: rs3764472
Type: single nucleotide variant
Location: chr18:66509032 (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

Disease context

CDH19-related disorder

Similar variants

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
CDH19 p.Cys19Ser 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-val597 (accessed [today's date]).

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