Is CDH8 p.Arg4= (c.10C>A) pathogenic?

CDH8 p.Arg4= (c.10C>A) is classified Likely benign in CDH8 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-06). Ultra-rare (popmax 0.0334%, afr).

How common is CDH8 p.Arg4= (c.10C>A) in the general population?

CDH8 p.Arg4= (c.10C>A) is ultra-rare (popmax 0.0334%, afr) (gnomAD).

CDH8 p.Arg4=

c.10C>A · rs139797882 · VCV749032

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, afr)

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 8.2	GERP 2.5, phastCons 1
Overall
CADD	12.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% African / African-American · 25/74,878 alleles

Filtering AF 0.0231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.00186% 30/1,609,122 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0334%	2,995
Remaining individualsnot grpmax-eligible	0.00481%	20,773
Admixed American	0.00335%	29,886

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: CDH8
Protein: p.Arg4=
Coding: c.10C>A
MANE Select: NM_001796
dbSNP: rs139797882
Type: single nucleotide variant
Location: chr16:62021394 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.26

Full CDH8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH8 p.Arg666Cys Likely benign ★★ same type
CDH8 p.Ile429= Benign ★★ same type
CDH8 p.Tyr667= Benign/Likely benign ★★ same type
CDH8 p.Ala30Thr Uncertain significance ★ ⚠ same type
CDH8 p.Ala332Thr Uncertain significance ★ ⚠ same type
CDH8 p.Ala443Thr Uncertain significance ★ ⚠ same type
CDH8 p.Ala502Gly Uncertain significance ★ ⚠ same type
CDH8 p.Ala629Val Uncertain significance ★ ⚠ 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/cdh8-p-arg4 (accessed [today's date]).

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