Is CELSR3 p.Pro1425= (c.4275C>T) pathogenic?

CELSR3 p.Pro1425= (c.4275C>T) is classified Likely benign in CELSR3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-08-13). Very rare (popmax 0.000935%, nfe); Associated with CELSR3-related disorder.

What condition is associated with CELSR3 p.Pro1425= (c.4275C>T)?

CELSR3 p.Pro1425= (c.4275C>T) is associated with CELSR3-related disorder (ClinVar).

How common is CELSR3 p.Pro1425= (c.4275C>T) in the general population?

CELSR3 p.Pro1425= (c.4275C>T) is very rare (popmax 0.000935%, nfe) (gnomAD).

CELSR3 p.Pro1425=

c.4275C>T · rs762689560 · VCV3052814

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000935%, nfe)

Conditions

CELSR3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -5.1	GERP -4.7
Overall
CADD	3.444	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000935% European (non-Finnish) · 11/1,176,846 alleles

Filtering AF 0.000502% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000367%

Overall 0.000684% 11/1,607,884 alleles · very rare exomes 11/1,455,510 · genomes 0/152,374 · joint denominator

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.Pro1425=
Coding: c.4275C>T
MANE Select: NM_001407
dbSNP: rs762689560
Type: single nucleotide variant
Location: chr3:48656822 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Residue 1425: the egf-like 1; calcium-binding domain

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

Disease context

CELSR3-related disorder

Similar variants

CELSR3 p.Phe282Ser Uncertain significance ★★ ⚠ same condition
CELSR3 p.Cys1502Tyr Uncertain significance ★ ⚠ same condition
CELSR3 p.Ala3148Glu Uncertain significance ⚠ same condition
CELSR3 c.7464-9T>C Likely benign same condition
CELSR3 c.8086-5T>G Likely benign same condition
CELSR3 c.8165+7T>C Likely benign same condition
CELSR3 c.9912-8G>A Likely benign same condition
CELSR3 c.*9C>T Likely benign 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/celsr3-p-pro1425 (accessed [today's date]).

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