Is CELSR1 p.Ser2964= (c.8892G>A) pathogenic?

CELSR1 p.Ser2964= (c.8892G>A) is classified Likely benign in CELSR1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-04-22). Ultra-rare (popmax 0.0329%, mid); Associated with CELSR1-related disorder.

What condition is associated with CELSR1 p.Ser2964= (c.8892G>A)?

CELSR1 p.Ser2964= (c.8892G>A) is associated with CELSR1-related disorder (ClinVar).

How common is CELSR1 p.Ser2964= (c.8892G>A) in the general population?

CELSR1 p.Ser2964= (c.8892G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

CELSR1 p.Ser2964=

c.8892G>A · rs375507061 · VCV3036476

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

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 -15	GERP -2.5
Overall
CADD	0.018	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,070 alleles

Filtering AF 0.00971% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00761%

Overall 0.00367% 59/1,607,532 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,035
African / African-American	0.0169%	5,901
Admixed American	0.01%	9,962
East Asian	0.00891%	11,220
South Asian	0.00439%	22,767
European (non-Finnish)	0.00254%	39,320
Remaining individualsnot grpmax-eligible	0.00161%	62,214

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.Ser2964=
Coding: c.8892G>A
MANE Select: NM_001378328
dbSNP: rs375507061
Type: single nucleotide variant
Location: chr22:46364139 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 2964: a UniProt-annotated variant site (in lmphm9); a UniProt-annotated variant site (in ntd; shows reduced protein localization to the cell membrane); the 'disordered' region

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

Disease context

CELSR1-related disorder

Similar variants

CELSR1 p.Ser2964Leu 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-ser2964 (accessed [today's date]).

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