Is CELSR2 p.Ala1114Val (c.3341C>T) pathogenic?

CELSR2 p.Ala1114Val (c.3341C>T) is classified Uncertain significance in CELSR2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-19). AlphaMissense: likely benign (0.0845); Very rare (popmax 0.00707%, nfe).

How common is CELSR2 p.Ala1114Val (c.3341C>T) in the general population?

CELSR2 p.Ala1114Val (c.3341C>T) is very rare (popmax 0.00707%, nfe) (gnomAD).

What do computational predictors say about CELSR2 p.Ala1114Val (c.3341C>T)?

AlphaMissense predicts likely benign (score 0.0845) — an in-silico prediction, not a clinical call.

CELSR2 p.Ala1114Val

c.3341C>T · rs776015230 · VCV1911350

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00707%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, REVEL

Computational evidence

Protein change
AlphaMissense	0.0845	likely benign
REVEL	0.115	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 0.95, phastCons 0.97
Regional constraint	o/e 0.77	unconstrained · MANE · 6,488 bp · p 1.6e-09 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00707% European (non-Finnish) · 83/1,174,046 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00536%

Overall 0.00562% 90/1,601,910 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00707%	14,145
Remaining individualsnot grpmax-eligible	0.00645%	15,503
South Asian	0.00225%	44,527
African / African-American	0.00134%	74,630

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.Ala1114Val
Coding: c.3341C>T
MANE Select: NM_001408
dbSNP: rs776015230
Type: single nucleotide variant
Location: chr1:109258462 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Residue 1114: the cadherin 9 domain

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

Similar variants

CELSR2 p.Ala1114= Likely benign ★ same residue
CELSR2 c.8338+1G>C 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-ala1114val (accessed [today's date]).

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