Is CELSR2 p.Leu17Pro (c.50T>C) pathogenic?

CELSR2 p.Leu17Pro (c.50T>C) is classified Likely benign in CELSR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-01). AlphaMissense: likely benign (0.1068); Rare (popmax 0.226%, eas).

How common is CELSR2 p.Leu17Pro (c.50T>C) in the general population?

CELSR2 p.Leu17Pro (c.50T>C) is rare (popmax 0.226%, eas) (gnomAD).

What do computational predictors say about CELSR2 p.Leu17Pro (c.50T>C)?

AlphaMissense predicts likely benign (score 0.1068) — an in-silico prediction, not a clinical call.

CELSR2 p.Leu17Pro

c.50T>C · rs200277265 · VCV1662312

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1068 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.226%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.1068	likely benign
REVEL	0.155	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.87	GERP -2.8, phastCons 0.047
Regional constraint	o/e 0.90	unconstrained · MANE · 1,783 bp · p 0.0042 · regional, not allelic
Overall
CADD	1.741	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.226% East Asian · 77/34,042 alleles

Filtering AF 0.186% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.17%

Overall 0.0471% 404/857,538 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.226%	442
Middle Eastern	0.0572%	1,749
Admixed American	0.0498%	2,008
African / African-American	0.045%	2,220
Remaining individualsnot grpmax-eligible	0.0446%	2,241
European (non-Finnish)	0.0422%	2,367
South Asian	0.03%	3,330
Finnishnot grpmax-eligible	0.0163%	6,129

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: CELSR2
Protein: p.Leu17Pro
Coding: c.50T>C
MANE Select: NM_001408
dbSNP: rs200277265
Type: single nucleotide variant
Location: chr1:109250129 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)

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-leu17pro (accessed [today's date]).

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