Is CDHR1 p.Val54Ile (c.160G>A) pathogenic?

CDHR1 p.Val54Ile (c.160G>A) is classified Uncertain significance in CDHR1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-21). AlphaMissense: likely benign (0.0727); Ultra-rare (popmax 0.0117%, amr); Associated with Inborn genetic diseases.

What condition is associated with CDHR1 p.Val54Ile (c.160G>A)?

CDHR1 p.Val54Ile (c.160G>A) is associated with Inborn genetic diseases (ClinVar).

How common is CDHR1 p.Val54Ile (c.160G>A) in the general population?

CDHR1 p.Val54Ile (c.160G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about CDHR1 p.Val54Ile (c.160G>A)?

AlphaMissense predicts likely benign (score 0.0727) — an in-silico prediction, not a clinical call.

CDHR1 p.Val54Ile

c.160G>A · rs138967568 · VCV1004486

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0727 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0727	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -5.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 4.8, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 20 kb · p 0.035 · regional, not allelic
Overall
CADD	19.02	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

Grpmax group 0.0117% Admixed American · 7/60,008 alleles

Filtering AF 0.00543% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00359% 58/1,614,046 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,573
Remaining individualsnot grpmax-eligible	0.0064%	15,622
European (non-Finnish)	0.00398%	25,107

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: CDHR1
Protein: p.Val54Ile
Coding: c.160G>A
MANE Select: NM_033100
dbSNP: rs138967568
Type: single nucleotide variant
Location: chr10:84196513 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 54: the cadherin 1 domain

Full CDHR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CDHR1 p.Ala106Thr Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala10Val Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala118Asp Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala132Val Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala292Asp Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala393Gly Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala493Val Uncertain significance ★★ ⚠ same condition
CDHR1 p.Ala793Thr Uncertain significance ★★ ⚠ 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/cdhr1-p-val54ile (accessed [today's date]).

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