Is CELSR3 p.Ala2792Val (c.8375C>T) pathogenic?

CELSR3 p.Ala2792Val (c.8375C>T) is classified Likely benign in CELSR3 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2023-10-23). AlphaMissense: likely benign (0.0732); Rare (popmax 0.19%, nfe); Associated with CELSR3-related disorder.

What condition is associated with CELSR3 p.Ala2792Val (c.8375C>T)?

CELSR3 p.Ala2792Val (c.8375C>T) is associated with CELSR3-related disorder (ClinVar).

How common is CELSR3 p.Ala2792Val (c.8375C>T) in the general population?

CELSR3 p.Ala2792Val (c.8375C>T) is rare (popmax 0.19%, nfe) (gnomAD).

What do computational predictors say about CELSR3 p.Ala2792Val (c.8375C>T)?

AlphaMissense predicts likely benign (score 0.0732) — an in-silico prediction, not a clinical call.

CELSR3 p.Ala2792Val

c.8375C>T · rs147947825 · VCV3033820

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0732 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.19%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Conditions

CELSR3-related disorder

Computational evidence

Protein change
AlphaMissense	0.0732	likely benign
REVEL	0.051	moderately benign-leaning
⇒ AlphaMissense and REVEL both call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.28 · evaluated, not missing
Constraint at this position
Conservation	phyloP -2.8	GERP -4.5
Regional constraint	o/e 0.92	unconstrained · MANE · 10 kb · p 0.0024 · regional, not allelic
Overall
CADD	4.141	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 0.19% European (non-Finnish) · 2,246/1,179,656 alleles

Filtering AF 0.184% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.181%

Overall 0.155% 2,498/1,612,492 alleles · rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.203%	492
European (non-Finnish)grpmax	0.19%	525
Finnishnot grpmax-eligible	0.0716%	1,396
South Asian	0.0417%	2,396
Admixed American	0.0317%	3,158
African / African-American	0.0293%	3,411
East Asian	0.00223%	44,868

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala2792Val
Coding: c.8375C>T
MANE Select: NM_001407
dbSNP: rs147947825
Type: single nucleotide variant
Location: chr3:48642998 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)

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

Disease context

CELSR3-related disorder

Similar variants

CELSR3 p.Phe282Ser Uncertain significance ★★ ⚠ same condition
CELSR3 p.Cys1502Tyr Uncertain significance ★ ⚠ same condition
CELSR3 p.Ala3148Glu Uncertain significance ⚠ same condition
CELSR3 c.7464-9T>C Likely benign same condition
CELSR3 c.8086-5T>G Likely benign same condition
CELSR3 c.8165+7T>C Likely benign same condition
CELSR3 c.9912-8G>A Likely benign same condition
CELSR3 c.*9C>T Likely benign same condition

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-ala2792val (accessed [today's date]).

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