Is CELSR2 p.Leu272Pro (c.815T>C) pathogenic?

CELSR2 p.Leu272Pro (c.815T>C) is classified Uncertain significance in CELSR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: likely pathogenic (0.6237); Absent from gnomAD v4.1.

How common is CELSR2 p.Leu272Pro (c.815T>C) in the general population?

CELSR2 p.Leu272Pro (c.815T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CELSR2 p.Leu272Pro (c.815T>C)?

AlphaMissense predicts likely pathogenic (score 0.6237) — an in-silico prediction, not a clinical call.

CELSR2 p.Leu272Pro

c.815T>C · VCV4651970

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6237 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.6237	likely pathogenic
REVEL	0.184	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 2	GERP -0.035, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 1,783 bp · p 0.0042 · regional, not allelic
Overall
CADD	24.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CELSR2
Protein: p.Leu272Pro
Coding: c.815T>C
MANE Select: NM_001408
Type: single nucleotide variant
Location: chr1:109250894 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Residue 272: the cadherin 1 domain

Full CELSR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELSR2 c.8338+1G>C Uncertain significance ★★ same type
CELSR2 p.Ala1114Val Uncertain significance ★★ ⚠ same type
CELSR2 p.Ala2145Thr Uncertain significance ★★ ⚠ same type
CELSR2 p.Ala2574Thr Uncertain significance ★★ ⚠ same type
CELSR2 p.Arg1171Gln Uncertain significance ★★ ⚠ same type
CELSR2 p.Arg1328His Uncertain significance ★★ ⚠ same type
CELSR2 p.Arg1400His Uncertain significance ★★ same type
CELSR2 p.Arg1978Gln 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/celsr2-p-leu272pro (accessed [today's date]).

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