Is CELSR3 p.Ile913Met (c.2739T>G) pathogenic?

CELSR3 p.Ile913Met (c.2739T>G) is classified Uncertain significance in CELSR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-20). AlphaMissense: ambiguous (0.5586); Rare (popmax 0.24%, afr).

How common is CELSR3 p.Ile913Met (c.2739T>G) in the general population?

CELSR3 p.Ile913Met (c.2739T>G) is rare (popmax 0.24%, afr) (gnomAD).

What do computational predictors say about CELSR3 p.Ile913Met (c.2739T>G)?

AlphaMissense predicts ambiguous (score 0.5586) — an in-silico prediction, not a clinical call.

CELSR3 p.Ile913Met

c.2739T>G · rs138035000 · VCV2398201

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5586 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.24%, afr)

Computational evidence

Protein change
AlphaMissense	0.5586	ambiguous
REVEL	0.397	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.68	GERP -0.5, phastCons 0.93
Regional constraint	o/e 0.69	unconstrained · MANE · 12 kb · p 9.5e-43 · regional, not allelic
Overall
CADD	22.2	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 0.24% African / African-American · 180/75,054 alleles

Filtering AF 0.211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.2%

Overall 0.0125% 201/1,614,208 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.24%	417
Admixed American	0.0217%	4,617
Remaining individualsnot grpmax-eligible	0.0096%	10,418
South Asian	0.0011%	91,082
European (non-Finnish)	8.47e-05%	1,180,036

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.Ile913Met
Coding: c.2739T>G
MANE Select: NM_001407
dbSNP: rs138035000
Type: single nucleotide variant
Location: chr3:48659896 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Residue 913: the cadherin 6 domain

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

Similar variants

CELSR3 p.Ala2862Val Uncertain significance ★★ ⚠ same type
CELSR3 p.Arg2345His Uncertain significance ★★ ⚠ same type
CELSR3 p.Gly2265Ser Uncertain significance ★★ ⚠ same type
CELSR3 p.Phe282Ser Uncertain significance ★★ ⚠ same type
CELSR3 p.Val1107Met Uncertain significance ★★ same type
CELSR3 p.Arg2886= Likely benign ★★ same type
CELSR3 p.Arg3189Gln Benign/Likely benign ★★ same type
CELSR3 p.Arg3201Gln Benign ★★ 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/celsr3-p-ile913met (accessed [today's date]).

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