Is CELSR3 p.Ala2279Val (c.6836C>T) pathogenic?

CELSR3 p.Ala2279Val (c.6836C>T) is classified Uncertain significance in CELSR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). AlphaMissense: likely benign (0.0862); Ultra-rare (popmax 0.0379%, nfe).

How common is CELSR3 p.Ala2279Val (c.6836C>T) in the general population?

CELSR3 p.Ala2279Val (c.6836C>T) is ultra-rare (popmax 0.0379%, nfe) (gnomAD).

What do computational predictors say about CELSR3 p.Ala2279Val (c.6836C>T)?

AlphaMissense predicts likely benign (score 0.0862) — an in-silico prediction, not a clinical call.

CELSR3 p.Ala2279Val

c.6836C>T · VCV3265803

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0862 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0379%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0862	likely benign
REVEL	0.089	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP 6.6	GERP 0.71, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 12 kb · p 9.5e-43 · regional, not allelic
Overall
CADD	19.34	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0379% European (non-Finnish) · 446/1,177,726 alleles

Filtering AF 0.0349% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0338%

Overall 0.0292% 470/1,607,240 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0379%	2,641
Remaining individualsnot grpmax-eligible	0.0177%	5,657
Middle Eastern	0.0166%	6,030
Admixed American	0.00842%	11,870
African / African-American	0.00668%	14,975
East Asian	0.00447%	22,348

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.Ala2279Val
Coding: c.6836C>T
MANE Select: NM_001407
Type: single nucleotide variant
Location: chr3:48648403 (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.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
CELSR3 p.Arg3201Gln 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-ala2279val (accessed [today's date]).

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