Is CELSR1 p.Pro2850Ser (c.8548C>T) pathogenic?

CELSR1 p.Pro2850Ser (c.8548C>T) is classified Uncertain significance in CELSR1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.1338); Very rare (popmax 0.00186%, nfe).

How common is CELSR1 p.Pro2850Ser (c.8548C>T) in the general population?

CELSR1 p.Pro2850Ser (c.8548C>T) is very rare (popmax 0.00186%, nfe) (gnomAD).

What do computational predictors say about CELSR1 p.Pro2850Ser (c.8548C>T)?

AlphaMissense predicts likely benign (score 0.1338) — an in-silico prediction, not a clinical call.

CELSR1 p.Pro2850Ser

c.8548C>T · rs1309847154 · VCV2257096

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1338 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00186%, nfe)

Computational evidence

Protein change
AlphaMissense	0.1338	likely benign
REVEL	0.414	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.5, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 46 kb · p 0.53 · regional, not allelic
Overall
CADD	23.4	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 0.00186% European (non-Finnish) · 22/1,179,852 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00155% 25/1,611,568 alleles · very rare exomes 24/1,459,320 · genomes 1/152,248 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00482%	20,758
European (non-Finnish)grpmax	0.00186%	53,630

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro2850Ser
Coding: c.8548C>T
MANE Select: NM_001378328
dbSNP: rs1309847154
Type: single nucleotide variant
Location: chr22:46365237 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 2850: a UniProt-annotated variant site (in lmphm9); the 'disordered' region

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

Similar variants

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
CELSR1 p.Arg1720Trp 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-pro2850ser (accessed [today's date]).

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