Is CELSR2 p.Ala2806Val (c.8417C>T) pathogenic?

CELSR2 p.Ala2806Val (c.8417C>T) is classified Benign in CELSR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-15). AlphaMissense: likely benign (0.0686); Low-frequency (popmax 4.88%, eas).

How common is CELSR2 p.Ala2806Val (c.8417C>T) in the general population?

CELSR2 p.Ala2806Val (c.8417C>T) is low-frequency (popmax 4.88%, eas) (gnomAD).

What do computational predictors say about CELSR2 p.Ala2806Val (c.8417C>T)?

AlphaMissense predicts likely benign (score 0.0686) — an in-silico prediction, not a clinical call.

CELSR2 p.Ala2806Val

c.8417C>T · rs77619489 · VCV1592188

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0686 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.88%, eas)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.0686	likely benign
REVEL	0.095	moderately 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 -1.1	GERP -3
Regional constraint	o/e 0.88	unconstrained · MANE · 15 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	8.066	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 4.88% East Asian · 2,190/44,854 alleles

Filtering AF 4.71% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.64%

Overall 0.411% 6,632/1,612,698 alleles · low-frequency exomes 6,017/1,460,454 · genomes 615/152,244 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	4.88%	20
South Asian	2.91%	34
Finnishnot grpmax-eligible	1.76%	57
Remaining individualsnot grpmax-eligible	0.53%	189
Middle Eastern	0.0495%	2,021
Admixed American	0.0301%	3,319
European (non-Finnish)	0.027%	3,697
African / African-American	0.00267%	37,491

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: CELSR2
Protein: p.Ala2806Val
Coding: c.8417C>T
MANE Select: NM_001408
dbSNP: rs77619489
Type: single nucleotide variant
Location: chr1:109273244 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Residue 2806: the 'disordered' region

Full CELSR2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELSR2 c.8338+1G>C Uncertain significance ★★ same type
CELSR2 p.Ala1114Val Uncertain significance ★★ ⚠ same type
CELSR2 p.Ala2145Thr Uncertain significance ★★ ⚠ same type
CELSR2 p.Ala2574Thr Uncertain significance ★★ ⚠ same type
CELSR2 p.Arg1171Gln Uncertain significance ★★ ⚠ same type
CELSR2 p.Arg1328His Uncertain significance ★★ ⚠ same type
CELSR2 p.Arg1400His Uncertain significance ★★ same type
CELSR2 p.Arg1978Gln 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/celsr2-p-ala2806val (accessed [today's date]).

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