Is CDHR1 p.Ile528Val (c.1582A>G) pathogenic?

CDHR1 p.Ile528Val (c.1582A>G) is classified Uncertain significance in CDHR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-05). AlphaMissense: likely benign (0.1563); Absent from gnomAD v4.1.

How common is CDHR1 p.Ile528Val (c.1582A>G) in the general population?

CDHR1 p.Ile528Val (c.1582A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CDHR1 p.Ile528Val (c.1582A>G)?

AlphaMissense predicts likely benign (score 0.1563) — an in-silico prediction, not a clinical call.

CDHR1 p.Ile528Val

c.1582A>G · rs2492537905 · VCV2133154

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1563 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1563	likely benign
REVEL	0.142	moderately benign-leaning
SaProt	LLR -7.91	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.7	GERP 4.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 20 kb · p 0.035 · regional, not allelic
Overall
CADD	21.2	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: CDHR1
Protein: p.Ile528Val
Coding: c.1582A>G
MANE Select: NM_033100
dbSNP: rs2492537905
Type: single nucleotide variant
Location: chr10:84212207 (GRCh38)
Gene constraint: LOEUF 1.004 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 78.79
Residue 528: the cadherin 5 domain

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

Similar variants

CDHR1 p.Ile528Thr Uncertain significance ★ ⚠ same residue
CDHR1 c.1168-1G>C Pathogenic/Likely pathogenic ★★ same type
CDHR1 c.1321-1G>A Likely pathogenic ★★ same type
CDHR1 c.1485+2T>C Pathogenic ★★ same type
CDHR1 c.1485+2T>G Pathogenic ★★ same type
CDHR1 c.1554-2A>C Pathogenic/Likely pathogenic ★★ same type
CDHR1 c.297+1G>T Pathogenic ★★ same type
CDHR1 c.525+1G>A Pathogenic ★★ 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/cdhr1-p-ile528val (accessed [today's date]).

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