Is CELSR1 p.Ile2107Val (c.6319A>G) pathogenic?

CELSR1 p.Ile2107Val (c.6319A>G) is classified Benign in CELSR1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2019-07-24). AlphaMissense: likely benign (0.0622); Common (popmax 65.4%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about CELSR1 p.Ile2107Val (c.6319A>G)?

AlphaMissense predicts likely benign (score 0.0622) — an in-silico prediction, not a clinical call.

CELSR1 p.Ile2107Val

Q: How common is CELSR1 p.Ile2107Val (c.6319A>G) in the general population?

CELSR1 p.Ile2107Val (c.6319A>G) is common (popmax 65.4%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.6319A>G · rs4044210 · VCV1264263

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0622 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 65.4%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0622	likely benign
REVEL	0.021	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 -5.4	GERP -3.2
Regional constraint	o/e 0.99	unconstrained · MANE · 46 kb · p 0.53 · regional, not allelic
Overall
CADD	0.03	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 65.4% African / African-American · 49,008/74,904 alleles

Filtering AF 64.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 64.7%

Overall 18.5% 298,399/1,612,724 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	65.4%	2
Amishnot grpmax-eligible	24.3%	4
Remaining individualsnot grpmax-eligible	18.3%	5
Ashkenazi Jewishnot grpmax-eligible	18.2%	5
European (non-Finnish)	17.2%	6
Middle Eastern	16.4%	6
South Asian	13.8%	7
Admixed American	12.1%	8
Finnishnot grpmax-eligible	11.7%	9
East Asian	1.7%	59

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.Ile2107Val
Coding: c.6319A>G
MANE Select: NM_001378328
dbSNP: rs4044210
Type: single nucleotide variant
Location: chr22:46390418 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)
Residue 2107: a UniProt-annotated variant site (in lmphm9); a UniProt-annotated variant site (in)

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-ile2107val (accessed [today's date]).

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