Is CELSR1 p.Ala1233= (c.3699C>G) pathogenic?

CELSR1 p.Ala1233= (c.3699C>G) is classified Benign in CELSR1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-29). Common (popmax 42.7%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CELSR1-related disorder.

What condition is associated with CELSR1 p.Ala1233= (c.3699C>G)?

CELSR1 p.Ala1233= (c.3699C>G) is associated with CELSR1-related disorder (ClinVar).

CELSR1 p.Ala1233=

Q: How common is CELSR1 p.Ala1233= (c.3699C>G) in the general population?

CELSR1 p.Ala1233= (c.3699C>G) is common (popmax 42.7%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.3699C>G · rs3747251 · VCV3055460

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 42.7%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

CELSR1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.012	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -20	GERP -3.5
Overall
CADD	0.164	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 42.7% African / African-American · 32,049/74,970 alleles

Filtering AF 42.4% ClinGen BA1/BS1 input FAF95, joint · FAF99 42.2%

Overall 4.96% 79,975/1,613,538 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	42.7%	2
East Asian	19%	5
Remaining individualsnot grpmax-eligible	5.97%	17
Admixed American	5.53%	18
Amishnot grpmax-eligible	4.61%	22
South Asian	4.21%	24
Finnishnot grpmax-eligible	3.33%	30
Middle Eastern	3.2%	31
Ashkenazi Jewishnot grpmax-eligible	2.39%	42
European (non-Finnish)	2.16%	46

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.Ala1233=
Coding: c.3699C>G
MANE Select: NM_001378328
dbSNP: rs3747251
Type: single nucleotide variant
Location: chr22:46464191 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 1233: a UniProt-annotated variant site (in lmphm9)

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

Disease context

CELSR1-related disorder

Similar variants

CELSR1 p.Ala1233Thr Likely benign ★ 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
CELSR1 p.Asp1201Asn Conflicting classifications of pathogenicity ★ 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-ala1233 (accessed [today's date]).

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