Is CELSR1 p.Val1518Phe (c.4552G>T) pathogenic?

CELSR1 p.Val1518Phe (c.4552G>T) is classified Likely benign in CELSR1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-19). AlphaMissense: likely benign (0.1815); Ultra-rare (popmax 0.0616%, nfe); Associated with CELSR1-related disorder.

What condition is associated with CELSR1 p.Val1518Phe (c.4552G>T)?

CELSR1 p.Val1518Phe (c.4552G>T) is associated with CELSR1-related disorder (ClinVar).

How common is CELSR1 p.Val1518Phe (c.4552G>T) in the general population?

CELSR1 p.Val1518Phe (c.4552G>T) is ultra-rare (popmax 0.0616%, nfe) (gnomAD).

What do computational predictors say about CELSR1 p.Val1518Phe (c.4552G>T)?

AlphaMissense predicts likely benign (score 0.1815) — an in-silico prediction, not a clinical call.

CELSR1 p.Val1518Phe

c.4552G>T · rs61737817 · VCV3047930

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1815 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0616%, nfe)

Conditions

CELSR1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1815	likely benign
REVEL	0.504	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.75, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 55 kb · p 0.079 · regional, not allelic
Overall
CADD	21.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0616% European (non-Finnish) · 727/1,179,966 alleles

Filtering AF 0.0579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0564%

Overall 0.0486% 785/1,614,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0616%	1,623
Middle Eastern	0.0495%	2,021
Remaining individualsnot grpmax-eligible	0.0464%	2,155
Finnishnot grpmax-eligible	0.0203%	4,921
African / African-American	0.00799%	12,508
Admixed American	0.00667%	15,002
South Asian	0.00329%	30,361

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.Val1518Phe
Coding: c.4552G>T
MANE Select: NM_001378328
dbSNP: rs61737817
Type: single nucleotide variant
Location: chr22:46433452 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 1518: a UniProt-annotated variant site (in lmphm9); the laminin g-like 1 domain

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

Disease context

CELSR1-related disorder

Similar variants

CELSR1 p.Val1518Leu Uncertain significance ★★ 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-val1518phe (accessed [today's date]).

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