Is CDH8 p.Ile429= (c.1287C>T) pathogenic?

CDH8 p.Ile429= (c.1287C>T) is classified Benign in CDH8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-11-26). Rare (popmax 0.64%, afr).

How common is CDH8 p.Ile429= (c.1287C>T) in the general population?

CDH8 p.Ile429= (c.1287C>T) is rare (popmax 0.64%, afr) (gnomAD).

CDH8 p.Ile429=

c.1287C>T · rs113978852 · VCV791104

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.64%, 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 -0.033	GERP -2.6, phastCons 0.2
Overall
CADD	8.039	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.64% African / African-American · 479/74,870 alleles

Filtering AF 0.592% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.574%

Overall 0.0328% 529/1,612,260 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.64%	156
Remaining individualsnot grpmax-eligible	0.0336%	2,973
Admixed American	0.0251%	3,983
Middle Eastern	0.0165%	6,052
South Asian	0.0055%	18,191
European (non-Finnish)	0.000679%	147,375

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.Ile429=
Coding: c.1287C>T
MANE Select: NM_001796
dbSNP: rs113978852
Type: single nucleotide variant
Location: chr16:61789473 (GRCh38)
Gene constraint: LOEUF 0.369 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 77.26
Residue 429: the cadherin 4 domain

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.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
CDH8 p.Arg123Lys 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-ile429 (accessed [today's date]).

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