Is CELSR2 p.Asn1168= (c.3504C>T) pathogenic?

CELSR2 p.Asn1168= (c.3504C>T) is classified Likely benign in CELSR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-04). Very rare (popmax 0.00121%, nfe).

How common is CELSR2 p.Asn1168= (c.3504C>T) in the general population?

CELSR2 p.Asn1168= (c.3504C>T) is very rare (popmax 0.00121%, nfe) (gnomAD).

CELSR2 p.Asn1168=

c.3504C>T · rs2526445584 · VCV2114090

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00121%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.48 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.27	GERP 0.95, phastCons 0.19
Overall
CADD	8.937	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00121% European (non-Finnish) · 14/1,157,054 alleles

Filtering AF 0.000702% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000549%

Overall 0.000988% 14/1,416,706 alleles · very rare

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: CELSR2
Protein: p.Asn1168=
Coding: c.3504C>T
MANE Select: NM_001408
dbSNP: rs2526445584
Type: single nucleotide variant
Location: chr1:109258625 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)

Full CELSR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELSR2 p.Asn1168Ser Uncertain significance ★ ⚠ same residue
CELSR2 c.8338+1G>C Uncertain significance ★★ same type
CELSR2 p.Ala1114Val Uncertain significance ★★ ⚠ same type
CELSR2 p.Ala2145Thr Uncertain significance ★★ ⚠ same type
CELSR2 p.Ala2574Thr Uncertain significance ★★ ⚠ same type
CELSR2 p.Arg1171Gln Uncertain significance ★★ ⚠ same type
CELSR2 p.Arg1328His Uncertain significance ★★ ⚠ same type
CELSR2 p.Arg1400His 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/celsr2-p-asn1168 (accessed [today's date]).

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