Is CELSR1 p.Asp1704= (c.5112C>T) pathogenic?

CELSR1 p.Asp1704= (c.5112C>T) is classified Benign in CELSR1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-25). Common (popmax 26.9%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CELSR1-related disorder.

What condition is associated with CELSR1 p.Asp1704= (c.5112C>T)?

CELSR1 p.Asp1704= (c.5112C>T) is associated with CELSR1-related disorder (ClinVar).

CELSR1 p.Asp1704=

Q: How common is CELSR1 p.Asp1704= (c.5112C>T) in the general population?

CELSR1 p.Asp1704= (c.5112C>T) is common (popmax 26.9%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5112C>T · rs35717986 · VCV3055245

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 26.9%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

CELSR1-related disorder

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 1.1	GERP -2, phastCons 0.81
Overall
CADD	5.107	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 26.9% African / African-American · 20,122/74,782 alleles

Filtering AF 26.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 26.5%

Overall 6.31% 101,724/1,612,768 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	26.9%	4
Ashkenazi Jewishnot grpmax-eligible	9.1%	11
Remaining individualsnot grpmax-eligible	6.55%	15
Finnishnot grpmax-eligible	5.61%	18
European (non-Finnish)	5.42%	18
Middle Eastern	5.19%	19
South Asian	4.89%	20
Admixed American	4.27%	23
Amishnot grpmax-eligible	2.97%	34
East Asian	0.00894%	11,188

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.Asp1704=
Coding: c.5112C>T
MANE Select: NM_001378328
dbSNP: rs35717986
Type: single nucleotide variant
Location: chr22:46409110 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 1704: a UniProt-annotated variant site (in lmphm9); the laminin g-like 2 domain

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

Disease context

CELSR1-related disorder

Similar variants

CELSR1 p.Arg1643Gln Uncertain significance ★★ ⚠ same condition
CELSR1 p.Pro46His Uncertain significance ★★ ⚠ same condition
CELSR1 p.Ser2825Leu Uncertain significance ★★ same condition
CELSR1 p.Val2338Ile Uncertain significance ★★ ⚠ same condition
CELSR1 p.Leu979Phe Likely pathogenic ★ ⚠ same condition
CELSR1 p.Ala2486Pro Uncertain significance ★ same condition
CELSR1 p.Asp1201Asn Conflicting classifications of pathogenicity ★ same condition
CELSR1 p.Cys1934= Uncertain significance ★ same condition

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-asp1704 (accessed [today's date]).

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