Is CELSR1 p.Ala41Val (c.122C>T) pathogenic?

CELSR1 p.Ala41Val (c.122C>T) is classified Uncertain significance in CELSR1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-21). AlphaMissense: likely benign (0.1112); Ultra-rare (popmax 0.0743%, amr).

How common is CELSR1 p.Ala41Val (c.122C>T) in the general population?

CELSR1 p.Ala41Val (c.122C>T) is ultra-rare (popmax 0.0743%, amr) (gnomAD).

What do computational predictors say about CELSR1 p.Ala41Val (c.122C>T)?

AlphaMissense predicts likely benign (score 0.1112) — an in-silico prediction, not a clinical call.

CELSR1 p.Ala41Val

c.122C>T · rs778668782 · VCV2359437

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1112 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0743%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Computational evidence

Protein change
AlphaMissense	0.1112	likely benign
REVEL	0.064	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 4.5	GERP -2.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 1,320 bp · p 0.15 · regional, not allelic
Overall
CADD	21.6	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 is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0743% Admixed American · 15/20,178 alleles

Filtering AF 0.0458% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.037%

Overall 0.00202% 22/1,088,418 alleles · ultra-rare exomes 5/940,608 · genomes 17/147,810 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0743%	1,345
Remaining individualsnot grpmax-eligible	0.00851%	11,752
African / African-American	0.00505%	19,786
European (non-Finnish)	0.000111%	897,376

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.Ala41Val
Coding: c.122C>T
MANE Select: NM_001378328
dbSNP: rs778668782
Type: single nucleotide variant
Location: chr22:46537049 (GRCh38)
Gene constraint: LOEUF 0.564 · pLI <0.01 (gnomAD)

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-ala41val (accessed [today's date]).

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