Is CELSR1 p.Ala29= (c.87C>G) pathogenic?

CELSR1 p.Ala29= (c.87C>G) is classified Likely benign in CELSR1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-03-14). Very rare (popmax 0.00553%, amr); Associated with CELSR1-related disorder.

What condition is associated with CELSR1 p.Ala29= (c.87C>G)?

CELSR1 p.Ala29= (c.87C>G) is associated with CELSR1-related disorder (ClinVar).

How common is CELSR1 p.Ala29= (c.87C>G) in the general population?

CELSR1 p.Ala29= (c.87C>G) is very rare (popmax 0.00553%, amr) (gnomAD).

CELSR1 p.Ala29=

c.87C>G · rs980266227 · VCV3029138

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00553%, amr)

Conditions

CELSR1-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 0.028	GERP -2.2, phastCons 0.66
Overall
CADD	9.838	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00553% Admixed American · 1/18,098 alleles

Overall 0.000678% 1/147,520 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: CELSR1
Protein: p.Ala29=
Coding: c.87C>G
MANE Select: NM_001378328
dbSNP: rs980266227
Type: single nucleotide variant
Location: chr22:46537084 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)

Full CELSR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CELSR1-related disorder

Similar variants

CELSR1 p.Ala29Val Uncertain significance ★ ⚠ same residue
ME2 p.Met29Thr Uncertain significance ★ ⚠ same residue
CELSR1 p.Arg1643Gln Uncertain significance ★★ ⚠ same condition
CELSR1 p.Pro46His Uncertain significance ★★ ⚠ same condition
CELSR1 p.Ser2825Leu Uncertain significance ★★ same condition
CELSR1 p.Val2338Ile Uncertain significance ★★ ⚠ same condition
CELSR1 p.Leu979Phe Likely pathogenic ★ ⚠ same condition
CELSR1 p.Ala2486Pro Uncertain significance ★ 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/celsr1-p-ala29 (accessed [today's date]).

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