Is CELSR3 p.Ala2292Val (c.6875C>T) pathogenic?

CELSR3 p.Ala2292Val (c.6875C>T) is classified Uncertain significance in CELSR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-22). AlphaMissense: likely benign (0.1007); Ultra-rare (popmax 0.0379%, eas).

How common is CELSR3 p.Ala2292Val (c.6875C>T) in the general population?

CELSR3 p.Ala2292Val (c.6875C>T) is ultra-rare (popmax 0.0379%, eas) (gnomAD).

What do computational predictors say about CELSR3 p.Ala2292Val (c.6875C>T)?

AlphaMissense predicts likely benign (score 0.1007) — an in-silico prediction, not a clinical call.

CELSR3 p.Ala2292Val

c.6875C>T · VCV3265812

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1007 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1007	likely benign
REVEL	0.08	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 12 kb · p 9.5e-43 · regional, not allelic
Overall
CADD	24.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0379% East Asian · 17/44,812 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.00242% 39/1,611,498 alleles · ultra-rare exomes 28/1,459,600 · genomes 11/151,898 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0379%	2,636
African / African-American	0.012%	8,322
Remaining individualsnot grpmax-eligible	0.0032%	31,208
South Asian	0.0022%	45,504
European (non-Finnish)	0.000763%	131,050

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.Ala2292Val
Coding: c.6875C>T
MANE Select: NM_001407
Type: single nucleotide variant
Location: chr3:48648364 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)

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

Similar variants

CELSR3 p.Ala2292Glu Uncertain significance ★ ⚠ same residue
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

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-ala2292val (accessed [today's date]).

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