Is CELSR1 p.Thr2124= (c.6372G>T) pathogenic?

CELSR1 p.Thr2124= (c.6372G>T) is classified Benign in CELSR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Common (popmax 6.62%, afr) — too common for a highly-penetrant pathogenic allele.

CELSR1 p.Thr2124=

Q: How common is CELSR1 p.Thr2124= (c.6372G>T) in the general population?

CELSR1 p.Thr2124= (c.6372G>T) is common (popmax 6.62%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6372G>T · rs34751339 · VCV777757

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 6.62%, 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 -11	GERP -3.5
Overall
CADD	0.073	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.62% African / African-American · 4,965/75,056 alleles

Filtering AF 6.46% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.4%

Overall 0.357% 5,755/1,613,316 alleles · common exomes 2,851/1,460,936 · genomes 2,904/152,380 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.62%	15
Remaining individualsnot grpmax-eligible	0.56%	179
Admixed American	0.486%	206
Middle Eastern	0.478%	209
South Asian	0.0274%	3,643
European (non-Finnish)	0.00797%	12,553

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.Thr2124=
Coding: c.6372G>T
MANE Select: NM_001378328
dbSNP: rs34751339
Type: single nucleotide variant
Location: chr22:46389473 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 2124: a UniProt-annotated variant site (in lmphm9)

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

Similar variants

CELSR1 p.Thr2124Met Uncertain significance ★ same residue
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

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-thr2124 (accessed [today's date]).

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