Is CELSR1 p.Ala773Val (c.2318C>T) pathogenic?

CELSR1 p.Ala773Val (c.2318C>T) is classified Benign in CELSR1 (ClinVar, Single submitter, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0959); Low-frequency (popmax 1.75%, afr).

How common is CELSR1 p.Ala773Val (c.2318C>T) in the general population?

CELSR1 p.Ala773Val (c.2318C>T) is low-frequency (popmax 1.75%, afr) (gnomAD).

What do computational predictors say about CELSR1 p.Ala773Val (c.2318C>T)?

AlphaMissense predicts likely benign (score 0.0959) — an in-silico prediction, not a clinical call.

CELSR1 p.Ala773Val

c.2318C>T · rs12170597 · VCV723717

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0959 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.75%, afr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0959	likely benign
REVEL	0.154	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 2.2	GERP -0.68, phastCons 0.96
Regional constraint	o/e 0.99	unconstrained · MANE · 71 kb · p 0.73 · regional, not allelic
Overall
CADD	8.793	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 1.75% African / African-American · 1,316/75,024 alleles

Filtering AF 1.68% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.64%

Overall 0.0921% 1,486/1,612,898 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.75%	57
Remaining individualsnot grpmax-eligible	0.0992%	1,008
Admixed American	0.0833%	1,200
Middle Eastern	0.0495%	2,020
East Asian	0.00891%	11,218
South Asian	0.00769%	13,012
European (non-Finnish)	0.00373%	26,818

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: CELSR1
Protein: p.Ala773Val
Coding: c.2318C>T
MANE Select: NM_001378328
dbSNP: rs12170597
Type: single nucleotide variant
Location: chr22:46534853 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 773: a UniProt-annotated variant site (in lmphm9); a UniProt-annotated variant site (in ntd; shows significantly reduced protein localization to the cell membrane); a β-strand; the cadherin 5 domain

Full CELSR1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELSR1 p.Ala2442Val Uncertain significance ★★ ⚠ same type
CELSR1 p.Ala2955Thr Uncertain significance ★★ ⚠ same type
CELSR1 p.Ala396Ser Uncertain significance ★★ ⚠ same type
CELSR1 p.Ala617Ser Uncertain significance ★★ ⚠ same type
CELSR1 p.Arg1323Gln Uncertain significance ★★ ⚠ same type
CELSR1 p.Arg1379His Uncertain significance ★★ ⚠ same type
CELSR1 p.Arg1643Gln Uncertain significance ★★ ⚠ same type
CELSR1 p.Arg1720Trp 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/celsr1-p-ala773val (accessed [today's date]).

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