Is CDH19 p.Glu752Lys (c.2254G>A) pathogenic?

CDH19 p.Glu752Lys (c.2254G>A) is classified Uncertain significance in CDH19 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-08). AlphaMissense: likely benign (0.129); Absent from gnomAD v4.1.

How common is CDH19 p.Glu752Lys (c.2254G>A) in the general population?

CDH19 p.Glu752Lys (c.2254G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDH19 p.Glu752Lys (c.2254G>A)?

AlphaMissense predicts likely benign (score 0.129) — an in-silico prediction, not a clinical call.

CDH19 p.Glu752Lys

c.2254G>A · rs199795370 · VCV2282772

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.129 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.129	likely benign
REVEL	0.304	indeterminate
SaProt	LLR -9.52	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 1.9, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 67 kb · p 0.00092 · regional, not allelic
Overall
CADD	22.2	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CDH19
Protein: p.Glu752Lys
Coding: c.2254G>A
MANE Select: NM_021153
dbSNP: rs199795370
Type: single nucleotide variant
Location: chr18:66504877 (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

CDH7 p.Ser752Arg Uncertain significance ★ ⚠ same residue
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

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-glu752lys (accessed [today's date]).

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