Is CELSR3 p.Arg1997Gln (c.5990G>A) pathogenic?

CELSR3 p.Arg1997Gln (c.5990G>A) is classified Uncertain significance in CELSR3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-05). AlphaMissense: likely benign (0.0653); Very rare (popmax 0.0081%, afr).

How common is CELSR3 p.Arg1997Gln (c.5990G>A) in the general population?

CELSR3 p.Arg1997Gln (c.5990G>A) is very rare (popmax 0.0081%, afr) (gnomAD).

What do computational predictors say about CELSR3 p.Arg1997Gln (c.5990G>A)?

AlphaMissense predicts likely benign (score 0.0653) — an in-silico prediction, not a clinical call.

CELSR3 p.Arg1997Gln

c.5990G>A · rs370929945 · VCV2357171

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0653 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0081%, afr)

Computational evidence

Protein change
AlphaMissense	0.0653	likely benign
REVEL	0.294	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -0.26, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 12 kb · p 9.5e-43 · regional, not allelic
Overall
CADD	24.5	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 0.0081% African / African-American · 6/74,094 alleles

Filtering AF 0.0035% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.000818% 13/1,589,214 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0081%	12,349
Admixed American	0.00179%	55,898
South Asian	0.00114%	87,726
European (non-Finnish)	0.000428%	233,669

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: CELSR3
Protein: p.Arg1997Gln
Coding: c.5990G>A
MANE Select: NM_001407
dbSNP: rs370929945
Type: single nucleotide variant
Location: chr3:48651652 (GRCh38)
Gene constraint: LOEUF 0.344 · pLI 1.00 (gnomAD)
Residue 1997: the egf-like 6; calcium-binding domain; a disulfide bond

Full CELSR3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELSR3 p.Ala2862Val Uncertain significance ★★ ⚠ same type
CELSR3 p.Arg2345His Uncertain significance ★★ ⚠ same type
CELSR3 p.Gly2265Ser Uncertain significance ★★ ⚠ same type
CELSR3 p.Phe282Ser Uncertain significance ★★ ⚠ same type
CELSR3 p.Val1107Met Uncertain significance ★★ same type
CELSR3 p.Arg2886= Likely benign ★★ same type
CELSR3 p.Arg3189Gln Benign/Likely benign ★★ same type
CELSR3 p.Arg3201Gln Benign ★★ 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/celsr3-p-arg1997gln (accessed [today's date]).

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