Is CDH19 p.Val167= (c.501T>C) pathogenic?

CDH19 p.Val167= (c.501T>C) is classified Benign in CDH19 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-24). Low-frequency (popmax 2.75%, afr); Associated with CDH19-related disorder.

What condition is associated with CDH19 p.Val167= (c.501T>C)?

CDH19 p.Val167= (c.501T>C) is associated with CDH19-related disorder (ClinVar).

How common is CDH19 p.Val167= (c.501T>C) in the general population?

CDH19 p.Val167= (c.501T>C) is low-frequency (popmax 2.75%, afr) (gnomAD).

CDH19 p.Val167=

c.501T>C · rs111743500 · VCV3043579

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 2.75%, afr)

Conditions

CDH19-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.034	GERP -5.9, phastCons 0.49
Overall
CADD	3.328	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.75% African / African-American · 2,056/74,836 alleles

Filtering AF 2.65% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.61%

Overall 0.177% 2,856/1,610,994 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.75%	36
South Asian	0.312%	320
Middle Eastern	0.298%	336
Remaining individualsnot grpmax-eligible	0.274%	365
Admixed American	0.231%	433
European (non-Finnish)	0.0156%	6,402
Ashkenazi Jewishnot grpmax-eligible	0.00678%	14,748
East Asian	0.00447%	22,392
Finnishnot grpmax-eligible	0.00156%	63,936

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.Val167=
Coding: c.501T>C
MANE Select: NM_021153
dbSNP: rs111743500
Type: single nucleotide variant
Location: chr18:66554514 (GRCh38)
Gene constraint: LOEUF 1.105 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 78.14
Residue 167: the cadherin 2 domain

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-val167 (accessed [today's date]).

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