Is CELSR3 p.Ile533Val (c.1597A>G) pathogenic?

CELSR3 p.Ile533Val (c.1597A>G) is classified Uncertain significance in CELSR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-06). AlphaMissense: likely benign (0.2577); Ultra-rare (popmax 0.0486%, nfe).

How common is CELSR3 p.Ile533Val (c.1597A>G) in the general population?

CELSR3 p.Ile533Val (c.1597A>G) is ultra-rare (popmax 0.0486%, nfe) (gnomAD).

What do computational predictors say about CELSR3 p.Ile533Val (c.1597A>G)?

AlphaMissense predicts likely benign (score 0.2577) — an in-silico prediction, not a clinical call.

CELSR3 p.Ile533Val

c.1597A>G · rs199908113 · VCV2399136

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2577 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0486%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.2577	likely benign
REVEL	0.192	benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 1,031 bp · p 5.2e-11 · regional, not allelic
Overall
CADD	25.0	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 0.0486% European (non-Finnish) · 574/1,180,042 alleles

Filtering AF 0.0453% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.044%

Overall 0.0361% 583/1,613,728 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0486%	2,056
Remaining individualsnot grpmax-eligible	0.0112%	8,926
African / African-American	0.00267%	37,477

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: CELSR3
Protein: p.Ile533Val
Coding: c.1597A>G
MANE Select: NM_001407
dbSNP: rs199908113
Type: single nucleotide variant
Location: chr3:48661038 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Residue 533: the cadherin 2 domain

Full CELSR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELSR3 p.Ala2862Val Uncertain significance ★★ ⚠ same type
CELSR3 p.Arg2345His Uncertain significance ★★ ⚠ same type
CELSR3 p.Gly2265Ser Uncertain significance ★★ ⚠ same type
CELSR3 p.Phe282Ser Uncertain significance ★★ ⚠ same type
CELSR3 p.Val1107Met Uncertain significance ★★ same type
CELSR3 p.Arg2886= Likely benign ★★ same type
CELSR3 p.Arg3189Gln Benign/Likely benign ★★ same type
CELSR3 p.Arg3201Gln Benign ★★ 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/celsr3-p-ile533val (accessed [today's date]).

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