Is CELSR1 p.Asp2907fs (c.8719dup) pathogenic?

CELSR1 p.Asp2907fs (c.8719dup) is classified Uncertain significance in CELSR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2020-01-17). Very rare (popmax 6.85e-05%).

How common is CELSR1 p.Asp2907fs (c.8719dup) in the general population?

CELSR1 p.Asp2907fs (c.8719dup) is very rare (popmax 6.85e-05%) (gnomAD).

CELSR1 p.Asp2907fs

c.8719dup · rs751828682 · VCV828040

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 6.85e-05%)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 33 of 35
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.97	GERP -0.11, phastCons 0.003

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.85e-05%

Overall 6.85e-05% 1/1,460,192 alleles · very rare

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.Asp2907fs
Coding: c.8719dup
MANE Select: NM_001378328
dbSNP: rs751828682
Type: Duplication
Location: chr22:46364571 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 2907: a UniProt-annotated variant site (in lmphm9); the 'disordered' region

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

Similar variants

CELSR1 p.Phe42fs Pathogenic ★ same type
CELSR1 p.Gly129_Ala130insThrGlyAlaArgLeuCysGly Conflicting classifications of pathogenicity ★ same type
CELSR1 p.Pro1329_Thr1334dup Uncertain significance ★ same type
CELSR1 p.Tyr1714fs Uncertain significance ★ same type
CELSR1 p.Ile1708fs Pathogenic same type

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-asp2907fs (accessed [today's date]).

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