Is CELSR1 p.Cys1934= (c.5802C>T) pathogenic?

CELSR1 p.Cys1934= (c.5802C>T) is classified Uncertain significance in CELSR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-17). Very rare (popmax 0.00673%, amr); Associated with CELSR1-related disorder.

What condition is associated with CELSR1 p.Cys1934= (c.5802C>T)?

CELSR1 p.Cys1934= (c.5802C>T) is associated with CELSR1-related disorder (ClinVar).

How common is CELSR1 p.Cys1934= (c.5802C>T) in the general population?

CELSR1 p.Cys1934= (c.5802C>T) is very rare (popmax 0.00673%, amr) (gnomAD).

CELSR1 p.Cys1934=

c.5802C>T · rs775270009 · VCV2636102

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00673%, amr)

Conditions

CELSR1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.56	donor gain · deltas
Constraint at this position
Conservation	phyloP -6.1	GERP -3
Overall
CADD	14.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00673% Admixed American · 4/59,420 alleles

Filtering AF 0.00386% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00353%

Overall 0.0046% 74/1,609,448 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00673%	14,855
Remaining individualsnot grpmax-eligible	0.00642%	15,577
Finnishnot grpmax-eligible	0.0063%	15,865
European (non-Finnish)	0.00492%	20,310
South Asian	0.00332%	30,143
East Asian	0.00223%	44,834

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.Cys1934=
Coding: c.5802C>T
MANE Select: NM_001378328
dbSNP: rs775270009
Type: single nucleotide variant
Location: chr22:46396646 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 1934: a UniProt-annotated variant site (in lmphm9); the egf-like 6; calcium-binding domain; a disulfide bond

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.Gly68Ser 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-cys1934 (accessed [today's date]).

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