Is CELSR1 p.Val987= (c.2961G>A) pathogenic?

CELSR1 p.Val987= (c.2961G>A) is classified Benign in CELSR1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-11-30). Common (popmax 25.2%, nfe) — too common for a highly-penetrant pathogenic allele.

CELSR1 p.Val987=

Q: How common is CELSR1 p.Val987= (c.2961G>A) in the general population?

CELSR1 p.Val987= (c.2961G>A) is common (popmax 25.2%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2961G>A · rs8141744 · VCV1263343

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 25.2%, nfe) — 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 0.28	GERP 1.9, phastCons 0.011
Overall
CADD	11.01	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 25.2% European (non-Finnish) · 297,272/1,179,986 alleles

Filtering AF 25.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 25.1%

Overall 23.3% 376,436/1,613,642 alleles · common exomes 342,215/1,461,476 · genomes 34,221/152,166 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	29%	3
European (non-Finnish)grpmax	25.2%	4
African / African-American	24.7%	4
Remaining individualsnot grpmax-eligible	21.9%	5
Finnishnot grpmax-eligible	21.1%	5
Ashkenazi Jewishnot grpmax-eligible	17.8%	6
South Asian	17.5%	6
Middle Eastern	16.2%	6
Admixed American	14%	7
East Asian	5.95%	17

Amish 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: CELSR1
Protein: p.Val987=
Coding: c.2961G>A
MANE Select: NM_001378328
dbSNP: rs8141744
Type: single nucleotide variant
Location: chr22:46534210 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 987: a UniProt-annotated variant site (in lmphm9); a β-strand; the cadherin 7 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-val987 (accessed [today's date]).

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