Is CELSR3 p.Phe2114= (c.6342C>T) pathogenic?

CELSR3 p.Phe2114= (c.6342C>T) is classified Likely benign in CELSR3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-09). Very rare (popmax 0.00167%, amr); Associated with CELSR3-related disorder.

What condition is associated with CELSR3 p.Phe2114= (c.6342C>T)?

CELSR3 p.Phe2114= (c.6342C>T) is associated with CELSR3-related disorder (ClinVar).

How common is CELSR3 p.Phe2114= (c.6342C>T) in the general population?

CELSR3 p.Phe2114= (c.6342C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

CELSR3 p.Phe2114=

c.6342C>T · rs868152619 · VCV3050563

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Conditions

CELSR3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.21	donor loss, 28 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 0.19	GERP -4.7, phastCons 0.25
Overall
CADD	7.088	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/59,996 alleles

Overall 0.000206% 3/1,458,854 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,996
South Asian	0.0011%	90,998
European (non-Finnish)	8.48e-05%	1,179,814

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: CELSR3
Protein: p.Phe2114=
Coding: c.6342C>T
MANE Select: NM_001407
dbSNP: rs868152619
Type: single nucleotide variant
Location: chr3:48650920 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Residue 2114: a disulfide bond; the laminin egf-like domain

Full CELSR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CELSR3-related disorder

Similar variants

CELSR3 p.Phe282Ser Uncertain significance ★★ ⚠ same condition
CELSR3 p.Cys1502Tyr Uncertain significance ★ ⚠ same condition
CELSR3 p.Ala3148Glu Uncertain significance ⚠ same condition
CELSR3 c.7464-9T>C Likely benign same condition
CELSR3 c.8086-5T>G Likely benign same condition
CELSR3 c.8165+7T>C Likely benign same condition
CELSR3 c.9912-8G>A Likely benign same condition
CELSR3 c.*9C>T Likely benign 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/celsr3-p-phe2114 (accessed [today's date]).

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