Is CELSR1 p.Glu1069Lys (c.3205G>A) pathogenic?

CELSR1 p.Glu1069Lys (c.3205G>A) is classified Uncertain significance in CELSR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-07-31). AlphaMissense: likely benign (0.1577); Absent from gnomAD v4.1.

How common is CELSR1 p.Glu1069Lys (c.3205G>A) in the general population?

CELSR1 p.Glu1069Lys (c.3205G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CELSR1 p.Glu1069Lys (c.3205G>A)?

AlphaMissense predicts likely benign (score 0.1577) — an in-silico prediction, not a clinical call.

CELSR1 p.Glu1069Lys

c.3205G>A · rs1555941126 · VCV450803

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1577 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.1577	likely benign
REVEL	0.328	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 71 kb · p 0.73 · regional, not allelic
Overall
CADD	24.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CELSR1
Protein: p.Glu1069Lys
Coding: c.3205G>A
MANE Select: NM_001378328
dbSNP: rs1555941126
Type: single nucleotide variant
Location: chr22:46533966 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 1069: a UniProt-annotated variant site (in lmphm9); the cadherin 8 domain

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

Similar variants

CELSR1 p.Ala2442Val Uncertain significance ★★ ⚠ same type
CELSR1 p.Ala2955Thr Uncertain significance ★★ ⚠ same type
CELSR1 p.Ala396Ser Uncertain significance ★★ ⚠ same type
CELSR1 p.Ala617Ser Uncertain significance ★★ ⚠ same type
CELSR1 p.Arg1323Gln Uncertain significance ★★ ⚠ same type
CELSR1 p.Arg1379His Uncertain significance ★★ ⚠ same type
CELSR1 p.Arg1643Gln Uncertain significance ★★ ⚠ same type
CELSR1 p.Arg1720Trp Uncertain significance ★★ ⚠ 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-glu1069lys (accessed [today's date]).

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