Is CELSR1 p.Val779Ile (c.2335G>A) pathogenic?

CELSR1 p.Val779Ile (c.2335G>A) is classified Benign in CELSR1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-05-29). AlphaMissense: likely benign (0.0757); Low-frequency (popmax 1.24%, eas); Associated with CELSR1-related disorder.

What condition is associated with CELSR1 p.Val779Ile (c.2335G>A)?

CELSR1 p.Val779Ile (c.2335G>A) is associated with CELSR1-related disorder (ClinVar).

How common is CELSR1 p.Val779Ile (c.2335G>A) in the general population?

CELSR1 p.Val779Ile (c.2335G>A) is low-frequency (popmax 1.24%, eas) (gnomAD).

What do computational predictors say about CELSR1 p.Val779Ile (c.2335G>A)?

AlphaMissense predicts likely benign (score 0.0757) — an in-silico prediction, not a clinical call.

CELSR1 p.Val779Ile

c.2335G>A · rs118087710 · VCV3047226

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0757 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.24%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

CELSR1-related disorder

Computational evidence

Protein change
AlphaMissense	0.0757	likely benign
REVEL	0.246	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 1.9	GERP -3.4, phastCons 0.94
Regional constraint	o/e 0.99	unconstrained · MANE · 71 kb · p 0.73 · regional, not allelic
Overall
CADD	17.23	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.24% East Asian · 558/44,874 alleles

Filtering AF 1.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.12%

Overall 0.213% 3,443/1,612,954 alleles · low-frequency exomes 2,929/1,460,662 · genomes 514/152,292 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	3.74%	27
East Asiangrpmax	1.24%	80
Remaining individualsnot grpmax-eligible	0.186%	539
South Asian	0.0659%	1,518
European (non-Finnish)	0.0297%	3,371
Admixed American	0.00833%	12,005
African / African-American	0.00267%	37,520

Finnish 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: CELSR1
Protein: p.Val779Ile
Coding: c.2335G>A
MANE Select: NM_001378328
dbSNP: rs118087710
Type: single nucleotide variant
Location: chr22:46534836 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 779: a UniProt-annotated variant site (in lmphm9); a β-strand; the cadherin 5 domain

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

Disease context

CELSR1-related disorder

Similar variants

CELSR1 p.Arg1643Gln Uncertain significance ★★ ⚠ same condition
CELSR1 p.Pro46His Uncertain significance ★★ ⚠ same condition
CELSR1 p.Ser2825Leu Uncertain significance ★★ same condition
CELSR1 p.Val2338Ile Uncertain significance ★★ ⚠ same condition
CELSR1 p.Leu979Phe Likely pathogenic ★ ⚠ same condition
CELSR1 p.Ala2486Pro Uncertain significance ★ same condition
CELSR1 p.Asp1201Asn Conflicting classifications of pathogenicity ★ same condition
CELSR1 p.Cys1934= Uncertain significance ★ 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/celsr1-p-val779ile (accessed [today's date]).

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