Is CELSR1 p.Ala82= (c.246G>C) pathogenic?

CELSR1 p.Ala82= (c.246G>C) is classified Likely benign in CELSR1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-04-27). Very rare (popmax 0.00105%, nfe); Associated with CELSR1-related disorder.

What condition is associated with CELSR1 p.Ala82= (c.246G>C)?

CELSR1 p.Ala82= (c.246G>C) is associated with CELSR1-related disorder (ClinVar).

How common is CELSR1 p.Ala82= (c.246G>C) in the general population?

CELSR1 p.Ala82= (c.246G>C) is very rare (popmax 0.00105%, nfe) (gnomAD).

CELSR1 p.Ala82=

c.246G>C · rs1476045941 · VCV3036194

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00105%, nfe)

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 -0.58	GERP -2.7
Overall
CADD	5.794	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00105% European (non-Finnish) · 10/950,920 alleles

Filtering AF 0.000532% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000388%

Overall 0.00102% 12/1,173,048 alleles · very rare exomes 10/1,024,772 · genomes 2/148,276 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00497%	20,109
European (non-Finnish)grpmax	0.00105%	95,092

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala82=
Coding: c.246G>C
MANE Select: NM_001378328
dbSNP: rs1476045941
Type: single nucleotide variant
Location: chr22:46536925 (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.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
CELSR1 p.Asp1201Asn Conflicting classifications of pathogenicity ★ same condition
CELSR1 p.Cys1934= 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-ala82 (accessed [today's date]).

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