Is CELSR2 p.Arg881Ter (c.2641C>T) pathogenic?

CELSR2 p.Arg881Ter (c.2641C>T) is classified Uncertain significance in CELSR2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-11-19). Very rare (popmax 8.47e-05%, nfe); Associated with CELSR2-related disorder.

What condition is associated with CELSR2 p.Arg881Ter (c.2641C>T)?

CELSR2 p.Arg881Ter (c.2641C>T) is associated with CELSR2-related disorder (ClinVar).

How common is CELSR2 p.Arg881Ter (c.2641C>T) in the general population?

CELSR2 p.Arg881Ter (c.2641C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

CELSR2 p.Arg881Ter

c.2641C>T · rs150322062 · VCV3059473

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

CELSR2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 1 of 34
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 1.1, phastCons 1
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,028 alleles

Overall 6.84e-05% 1/1,461,688 alleles · very rare

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: CELSR2
Protein: p.Arg881Ter
Coding: c.2641C>T
MANE Select: NM_001408
dbSNP: rs150322062
Type: single nucleotide variant
Location: chr1:109252720 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Residue 881: the cadherin 7 domain

Full CELSR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CELSR2-related disorder

Similar variants

CELSR2 p.Arg426Ter Uncertain significance same condition
CELSR2 p.Ala2579= Likely benign same condition
CELSR2 p.Arg2015= Benign same condition
CELSR2 p.Arg2191His Likely benign same condition
CELSR2 p.Asn1182= Likely benign same condition
CELSR2 p.Asn1830= Likely benign same condition
CELSR2 p.Gln2053= Likely benign same condition
CELSR2 p.Ile2250= 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/celsr2-p-arg881ter (accessed [today's date]).

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