Is CELSR3 p.Pro1306Leu (c.3917C>T) pathogenic?

CELSR3 p.Pro1306Leu (c.3917C>T) is classified Uncertain significance in CELSR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-07). AlphaMissense: likely benign (0.3174); Rare (popmax 0.222%, sas).

How common is CELSR3 p.Pro1306Leu (c.3917C>T) in the general population?

CELSR3 p.Pro1306Leu (c.3917C>T) is rare (popmax 0.222%, sas) (gnomAD).

What do computational predictors say about CELSR3 p.Pro1306Leu (c.3917C>T)?

AlphaMissense predicts likely benign (score 0.3174) — an in-silico prediction, not a clinical call.

CELSR3 p.Pro1306Leu

c.3917C>T · rs564290921 · VCV2460207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3174 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.222%, sas)

Computational evidence

Protein change
AlphaMissense	0.3174	likely benign
REVEL	0.491	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.3, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 12 kb · p 9.5e-43 · regional, not allelic
Overall
CADD	24.7	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

Grpmax group 0.222% South Asian · 202/91,086 alleles

Filtering AF 0.197% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.187%

Overall 0.0129% 209/1,613,986 alleles · rare exomes 193/1,461,656 · genomes 16/152,330 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.222%	451
Remaining individualsnot grpmax-eligible	0.008%	12,498
European (non-Finnish)	0.000169%	589,977

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.Pro1306Leu
Coding: c.3917C>T
MANE Select: NM_001407
dbSNP: rs564290921
Type: single nucleotide variant
Location: chr3:48657180 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)

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-pro1306leu (accessed [today's date]).

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