Is CELSR3 p.Ala1304= (c.3912T>C) pathogenic?

CELSR3 p.Ala1304= (c.3912T>C) is classified Likely benign in CELSR3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-28). Very rare (popmax 0.00333%, amr); Associated with CELSR3-related disorder.

What condition is associated with CELSR3 p.Ala1304= (c.3912T>C)?

CELSR3 p.Ala1304= (c.3912T>C) is associated with CELSR3-related disorder (ClinVar).

How common is CELSR3 p.Ala1304= (c.3912T>C) in the general population?

CELSR3 p.Ala1304= (c.3912T>C) is very rare (popmax 0.00333%, amr) (gnomAD).

CELSR3 p.Ala1304=

c.3912T>C · rs745321300 · VCV3058341

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

CELSR3-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -1.1, phastCons 1
Overall
CADD	5.05	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,004 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000496% 8/1,613,816 alleles · very rare exomes 6/1,461,608 · genomes 2/152,208 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,002
African / African-American	0.00133%	74,924
European (non-Finnish)	0.000424%	235,988

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.Ala1304=
Coding: c.3912T>C
MANE Select: NM_001407
dbSNP: rs745321300
Type: single nucleotide variant
Location: chr3:48657185 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)

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

Disease context

CELSR3-related disorder

Similar variants

CELSR3 p.Phe282Ser Uncertain significance ★★ ⚠ same condition
CELSR3 p.Cys1502Tyr Uncertain significance ★ ⚠ same condition
CELSR3 p.Ala3148Glu Uncertain significance ⚠ same condition
CELSR3 c.7464-9T>C Likely benign same condition
CELSR3 c.8086-5T>G Likely benign same condition
CELSR3 c.8165+7T>C Likely benign same condition
CELSR3 c.9912-8G>A Likely benign same condition
CELSR3 c.*9C>T Likely benign 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/celsr3-p-ala1304 (accessed [today's date]).

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