Is CELSR2 p.Ala1849Val (c.5546C>T) pathogenic?

CELSR2 p.Ala1849Val (c.5546C>T) is classified Benign in CELSR2 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-01-25). AlphaMissense: likely benign (0.1121); Low-frequency (popmax 1.58%, afr).

How common is CELSR2 p.Ala1849Val (c.5546C>T) in the general population?

CELSR2 p.Ala1849Val (c.5546C>T) is low-frequency (popmax 1.58%, afr) (gnomAD).

What do computational predictors say about CELSR2 p.Ala1849Val (c.5546C>T)?

AlphaMissense predicts likely benign (score 0.1121) — an in-silico prediction, not a clinical call.

CELSR2 p.Ala1849Val

c.5546C>T · rs115193384 · VCV1576312

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1121 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.58%, afr)

Computational evidence

Protein change
AlphaMissense	0.1121	likely benign
REVEL	0.303	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	GERP -0.16, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 15 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	22.0	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 1.58% African / African-American · 1,189/75,030 alleles

Filtering AF 1.51% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.48%

Overall 0.0835% 1,348/1,614,154 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.58%	63
Admixed American	0.108%	923
Remaining individualsnot grpmax-eligible	0.088%	1,136
Middle Eastern	0.0165%	6,062
South Asian	0.00329%	30,361
European (non-Finnish)	0.00288%	34,707
East Asian	0.00223%	44,888

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.Ala1849Val
Coding: c.5546C>T
MANE Select: NM_001408
dbSNP: rs115193384
Type: single nucleotide variant
Location: chr1:109264949 (GRCh38)
Gene constraint: LOEUF 0.396 · pLI 1.00 (gnomAD)
Residue 1849: the egf-like 6; calcium-binding domain; a disulfide bond

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-ala1849val (accessed [today's date]).

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