Is CELSR3 p.Val1107Met (c.3319G>A) pathogenic?

CELSR3 p.Val1107Met (c.3319G>A) is classified Uncertain significance in CELSR3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-19). AlphaMissense: ambiguous (0.509); Ultra-rare (popmax 0.0164%, mid).

How common is CELSR3 p.Val1107Met (c.3319G>A) in the general population?

CELSR3 p.Val1107Met (c.3319G>A) is ultra-rare (popmax 0.0164%, mid) (gnomAD).

What do computational predictors say about CELSR3 p.Val1107Met (c.3319G>A)?

AlphaMissense predicts ambiguous (score 0.509) — an in-silico prediction, not a clinical call.

CELSR3 p.Val1107Met

c.3319G>A · VCV3831400

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.509 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0164%, mid)

Computational evidence

Protein change
AlphaMissense	0.509	ambiguous
REVEL	0.354	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.5, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 12 kb · p 9.5e-43 · regional, not allelic
Overall
CADD	27.6	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 0.0164% Middle Eastern · 1/6,084 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.00285% 46/1,614,068 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0164%	6,084
African / African-American	0.00801%	12,487
South Asian	0.00329%	30,361
European (non-Finnish)	0.00288%	34,707
Admixed American	0.00167%	60,002
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Val1107Met
Coding: c.3319G>A
MANE Select: NM_001407
Type: single nucleotide variant
Location: chr3:48659316 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Residue 1107: the cadherin 8 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.Arg2886= Likely benign ★★ same type
CELSR3 p.Arg3189Gln Benign/Likely benign ★★ same type
CELSR3 p.Arg3201Gln Benign ★★ same type
CELSR3 p.Asn1770= Likely 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-val1107met (accessed [today's date]).

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