Is CELSR1 p.Thr607= (c.1821G>A) pathogenic?

CELSR1 p.Thr607= (c.1821G>A) is classified Benign in CELSR1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-29). Common (popmax 16.2%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CELSR1-related disorder.

What condition is associated with CELSR1 p.Thr607= (c.1821G>A)?

CELSR1 p.Thr607= (c.1821G>A) is associated with CELSR1-related disorder (ClinVar).

CELSR1 p.Thr607=

Q: How common is CELSR1 p.Thr607= (c.1821G>A) in the general population?

CELSR1 p.Thr607= (c.1821G>A) is common (popmax 16.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1821G>A · rs35637956 · VCV3055342

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 16.2%, 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 -9.9	GERP -3.2
Overall
CADD	0.453	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 16.2% African / African-American · 12,157/75,044 alleles

Filtering AF 16% ClinGen BA1/BS1 input FAF95, joint · FAF99 15.9%

Overall 0.882% 14,222/1,612,330 alleles · common exomes 7,141/1,460,016 · genomes 7,081/152,314 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	16.2%	6
Remaining individualsnot grpmax-eligible	1.29%	77
Admixed American	1.14%	88
Middle Eastern	0.924%	108
Ashkenazi Jewishnot grpmax-eligible	0.071%	1,408
South Asian	0.0571%	1,751
European (non-Finnish)	0.0375%	2,663
East Asian	0.00223%	44,884
Finnishnot grpmax-eligible	0.0016%	62,432

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.Thr607=
Coding: c.1821G>A
MANE Select: NM_001378328
dbSNP: rs35637956
Type: single nucleotide variant
Location: chr22:46535350 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 607: 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

Disease context

CELSR1-related disorder

Similar variants

CELSR1 p.Thr607Met Uncertain significance ★ ⚠ same residue
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

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-thr607 (accessed [today's date]).

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