Is CELSR1 p.Pro2987= (c.8961G>A) pathogenic?

CELSR1 p.Pro2987= (c.8961G>A) is classified Benign in CELSR1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-12-31). Common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele.

CELSR1 p.Pro2987=

Q: How common is CELSR1 p.Pro2987= (c.8961G>A) in the general population?

CELSR1 p.Pro2987= (c.8961G>A) is common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.8961G>A · rs28495011 · VCV782760

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 10.1%, afr) — too common for a highly-penetrant pathogenic allele

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 -12	GERP -2.5
Overall
CADD	0.136	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.1% African / African-American · 7,605/75,020 alleles

Filtering AF 9.95% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.87%

Overall 0.574% 9,256/1,612,320 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.1%	10
Admixed American	0.783%	128
Remaining individualsnot grpmax-eligible	0.749%	133
Middle Eastern	0.612%	164
Ashkenazi Jewishnot grpmax-eligible	0.47%	213
South Asian	0.0812%	1,231
European (non-Finnish)	0.0381%	2,627
East Asian	0.0312%	3,205

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.Pro2987=
Coding: c.8961G>A
MANE Select: NM_001378328
dbSNP: rs28495011
Type: single nucleotide variant
Location: chr22:46364070 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 2987: a UniProt-annotated variant site (in lmphm9); the 'disordered' region

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-pro2987 (accessed [today's date]).

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