Is CELSR1 p.Asp627= (c.1881C>T) pathogenic?

CELSR1 p.Asp627= (c.1881C>T) is classified Benign/Likely benign in CELSR1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-10-31). Rare (popmax 0.332%, amr).

How common is CELSR1 p.Asp627= (c.1881C>T) in the general population?

CELSR1 p.Asp627= (c.1881C>T) is rare (popmax 0.332%, amr) (gnomAD).

CELSR1 p.Asp627=

c.1881C>T · rs56207834 · VCV774541

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.332%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.069	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.3	GERP -0.63, phastCons 0.98
Overall
CADD	1.364	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.332% Admixed American · 199/60,024 alleles

Filtering AF 0.294% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.279%

Overall 0.128% 2,065/1,611,130 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.332%	302
European (non-Finnish)	0.145%	690
Remaining individualsnot grpmax-eligible	0.12%	833
Middle Eastern	0.066%	1,516
Finnishnot grpmax-eligible	0.0442%	2,260
South Asian	0.0351%	2,846
African / African-American	0.024%	4,170

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: CELSR1
Protein: p.Asp627=
Coding: c.1881C>T
MANE Select: NM_001378328
dbSNP: rs56207834
Type: single nucleotide variant
Location: chr22:46535290 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 627: a UniProt-annotated variant site (in lmphm9); the cadherin 4 domain

Full CELSR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELSR1 p.Ala2442Val Uncertain significance ★★ ⚠ same type
CELSR1 p.Ala2955Thr Uncertain significance ★★ ⚠ same type
CELSR1 p.Ala396Ser Uncertain significance ★★ ⚠ same type
CELSR1 p.Ala617Ser Uncertain significance ★★ ⚠ same type
CELSR1 p.Arg1323Gln Uncertain significance ★★ ⚠ same type
CELSR1 p.Arg1379His Uncertain significance ★★ ⚠ same type
CELSR1 p.Arg1643Gln Uncertain significance ★★ ⚠ same type
CELSR1 p.Arg1720Trp 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/celsr1-p-asp627 (accessed [today's date]).

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