Is CDH16 p.Val29Phe (c.85G>T) pathogenic?

CDH16 p.Val29Phe (c.85G>T) is classified Uncertain significance in CDH16 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: ambiguous (0.3976); Ultra-rare (popmax 0.0273%, nfe).

How common is CDH16 p.Val29Phe (c.85G>T) in the general population?

CDH16 p.Val29Phe (c.85G>T) is ultra-rare (popmax 0.0273%, nfe) (gnomAD).

What do computational predictors say about CDH16 p.Val29Phe (c.85G>T)?

AlphaMissense predicts ambiguous (score 0.3976) — an in-silico prediction, not a clinical call.

CDH16 p.Val29Phe

c.85G>T · rs143000205 · VCV3141146

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3976 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0273%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3976	ambiguous
REVEL	0.459	indeterminate
SaProt	LLR -10.41	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 0.31, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 9,670 bp · p 0.11 · regional, not allelic
Overall
CADD	20.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0273% European (non-Finnish) · 322/1,179,776 alleles

Filtering AF 0.0248% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0239%

Overall 0.021% 338/1,613,364 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0273%	3,664
Remaining individualsnot grpmax-eligible	0.016%	6,246
Admixed American	0.00501%	19,967
African / African-American	0.004%	24,977

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: CDH16
Protein: p.Val29Phe
Coding: c.85G>T
MANE Select: NM_004062
dbSNP: rs143000205
Type: single nucleotide variant
Location: chr16:66917686 (GRCh38)
Gene constraint: LOEUF 1.079 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.17
Residue 29: the cadherin 1 domain

Full CDH16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDH16 p.Arg717His Benign ★★ same type
CDH16 p.Leu377= Benign ★★ same type
CDH16 p.Ala133Ser Uncertain significance ★ ⚠ same type
CDH16 p.Ala159Val Uncertain significance ★ ⚠ same type
CDH16 p.Ala173Thr Uncertain significance ★ ⚠ same type
CDH16 p.Ala202Val Uncertain significance ★ ⚠ same type
CDH16 p.Ala20Thr Uncertain significance ★ ⚠ same type
CDH16 p.Ala23Thr 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/cdh16-p-val29phe (accessed [today's date]).

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