Is CELSR3 p.Ser860Arg (c.2580T>G) pathogenic?

CELSR3 p.Ser860Arg (c.2580T>G) is classified Benign in CELSR3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-15). AlphaMissense: likely pathogenic (0.9004); Low-frequency (popmax 1.74%, afr).

How common is CELSR3 p.Ser860Arg (c.2580T>G) in the general population?

CELSR3 p.Ser860Arg (c.2580T>G) is low-frequency (popmax 1.74%, afr) (gnomAD).

What do computational predictors say about CELSR3 p.Ser860Arg (c.2580T>G)?

AlphaMissense predicts likely pathogenic (score 0.9004) — an in-silico prediction, not a clinical call.

CELSR3 p.Ser860Arg

c.2580T>G · rs142475235 · VCV715568

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9004 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.74%, afr)

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.9004	likely pathogenic
REVEL	0.199	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense calls this damaging; REVEL does not; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.22	GERP -4.5, phastCons 0.001
Regional constraint	o/e 0.89	unconstrained · MANE · 541 bp · p 0.092 · regional, not allelic
Overall
CADD	18.65	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.74% African / African-American · 1,304/75,030 alleles

Filtering AF 1.66% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.63%

Overall 0.0999% 1,612/1,614,208 alleles · low-frequency exomes 877/1,461,890 · genomes 735/152,318 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.74%	58
Admixed American	0.17%	589
Remaining individualsnot grpmax-eligible	0.15%	665
Middle Eastern	0.115%	866
European (non-Finnish)	0.00839%	11,920
South Asian	0.00659%	15,181

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: CELSR3
Protein: p.Ser860Arg
Coding: c.2580T>G
MANE Select: NM_001407
dbSNP: rs142475235
Type: single nucleotide variant
Location: chr3:48660055 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Residue 860: the cadherin 6 domain

Full CELSR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELSR3 p.Ala2862Val Uncertain significance ★★ ⚠ same type
CELSR3 p.Arg2345His Uncertain significance ★★ ⚠ same type
CELSR3 p.Gly2265Ser Uncertain significance ★★ ⚠ same type
CELSR3 p.Phe282Ser Uncertain significance ★★ ⚠ same type
CELSR3 p.Val1107Met Uncertain significance ★★ same type
CELSR3 p.Arg2886= Likely benign ★★ same type
CELSR3 p.Arg3189Gln Benign/Likely benign ★★ same type
CELSR3 p.Arg3201Gln Benign ★★ 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/celsr3-p-ser860arg (accessed [today's date]).

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