Is CELSR1 p.Thr2147= (c.6441G>A) pathogenic?

CELSR1 p.Thr2147= (c.6441G>A) is classified Benign in CELSR1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-03). Common (popmax 11.8%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CELSR1-related disorder.

What condition is associated with CELSR1 p.Thr2147= (c.6441G>A)?

CELSR1 p.Thr2147= (c.6441G>A) is associated with CELSR1-related disorder (ClinVar).

CELSR1 p.Thr2147=

Q: How common is CELSR1 p.Thr2147= (c.6441G>A) in the general population?

CELSR1 p.Thr2147= (c.6441G>A) is common (popmax 11.8%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6441G>A · rs11090875 · VCV3055631

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 11.8%, 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 -12	GERP -3.2
Overall
CADD	0.382	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.8% African / African-American · 8,876/75,050 alleles

Filtering AF 11.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 11.5%

Overall 8.51% 137,187/1,612,144 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	11.8%	8
Ashkenazi Jewishnot grpmax-eligible	10.6%	9
European (non-Finnish)	9.04%	11
Amishnot grpmax-eligible	8.11%	12
Remaining individualsnot grpmax-eligible	7.96%	13
Middle Eastern	7.24%	14
Finnishnot grpmax-eligible	6.98%	14
South Asian	6.28%	16
Admixed American	4.95%	20
East Asian	0.0201%	4,987

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.Thr2147=
Coding: c.6441G>A
MANE Select: NM_001378328
dbSNP: rs11090875
Type: single nucleotide variant
Location: chr22:46389404 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 2147: a UniProt-annotated variant site (in lmphm9)

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

Disease context

CELSR1-related disorder

Similar variants

CELSR1 p.Thr2147Lys Uncertain significance ★ ⚠ same residue
CELSR1 p.Thr2147Met 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

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-thr2147 (accessed [today's date]).

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