Is CELSR3 p.Arg1048Trp (c.3142C>T) pathogenic?

CELSR3 p.Arg1048Trp (c.3142C>T) is classified Likely pathogenic in CELSR3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-08-16). AlphaMissense: likely benign (0.2111); Ultra-rare (popmax 0.0156%, eas); Associated with congenital anomalies of kidney and urinary tract 1.

What condition is associated with CELSR3 p.Arg1048Trp (c.3142C>T)?

CELSR3 p.Arg1048Trp (c.3142C>T) is associated with congenital anomalies of kidney and urinary tract 1 (ClinVar).

How common is CELSR3 p.Arg1048Trp (c.3142C>T) in the general population?

CELSR3 p.Arg1048Trp (c.3142C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about CELSR3 p.Arg1048Trp (c.3142C>T)?

AlphaMissense predicts likely benign (score 0.2111) — an in-silico prediction, not a clinical call.

CELSR3 p.Arg1048Trp

c.3142C>T · rs560173014 · VCV2672065

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2111 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Conditions

congenital anomalies of kidney and urinary tract 1

Computational evidence

Protein change
AlphaMissense	0.2111	likely benign ⚠ discordant with ClinVar
REVEL	0.357	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -1.2, phastCons 0.89
Regional constraint	o/e 0.69	unconstrained · MANE · 12 kb · p 9.5e-43 · regional, not allelic
Overall
CADD	22.5	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 0.0156% East Asian · 7/44,890 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.00136% 22/1,614,198 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,413
African / African-American	0.00133%	75,048
European (non-Finnish)	0.0011%	90,772
South Asian	0.0011%	91,084

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.Arg1048Trp
Coding: c.3142C>T
MANE Select: NM_001407
dbSNP: rs560173014
Type: single nucleotide variant
Location: chr3:48659493 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Residue 1048: the cadherin 7 domain

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

Disease context

congenital anomalies of kidney and urinary tract 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CELSR3 p.Glu1034Gln Likely pathogenic ⚠ same condition
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

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-arg1048trp (accessed [today's date]).

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