Is CELSR3 p.Asn1770= (c.5310C>T) pathogenic?

CELSR3 p.Asn1770= (c.5310C>T) is classified Likely benign in CELSR3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-30). Ultra-rare (popmax 0.0583%, nfe).

How common is CELSR3 p.Asn1770= (c.5310C>T) in the general population?

CELSR3 p.Asn1770= (c.5310C>T) is ultra-rare (popmax 0.0583%, nfe) (gnomAD).

CELSR3 p.Asn1770=

c.5310C>T · rs146204269 · VCV1298916

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0583%, nfe)

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 -4.9	GERP -4.1
Overall
CADD	3.145	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0583% European (non-Finnish) · 688/1,180,036 alleles

Filtering AF 0.0546% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0532%

Overall 0.0509% 822/1,614,194 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.106%	941
European (non-Finnish)grpmax	0.0583%	1,715
Remaining individualsnot grpmax-eligible	0.0464%	2,156
African / African-American	0.0253%	3,950
Admixed American	0.015%	6,670
South Asian	0.00878%	11,386
East Asian	0.00223%	44,888

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asn1770=
Coding: c.5310C>T
MANE Select: NM_001407
dbSNP: rs146204269
Type: single nucleotide variant
Location: chr3:48653757 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Residue 1770: the laminin g-like 2 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-asn1770 (accessed [today's date]).

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