Is CELF1 p.Arg152Gln (c.455G>A) pathogenic?

CELF1 p.Arg152Gln (c.455G>A) is classified Uncertain significance in CELF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-23). AlphaMissense: ambiguous (0.4244); Very rare (popmax 0.0022%, sas).

How common is CELF1 p.Arg152Gln (c.455G>A) in the general population?

CELF1 p.Arg152Gln (c.455G>A) is very rare (popmax 0.0022%, sas) (gnomAD).

What do computational predictors say about CELF1 p.Arg152Gln (c.455G>A)?

AlphaMissense predicts ambiguous (score 0.4244) — an in-silico prediction, not a clinical call.

CELF1 p.Arg152Gln

c.455G>A · rs776176922 · VCV2468207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4244 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0022%, sas)

Computational evidence

Protein change
AlphaMissense	0.4244	ambiguous
REVEL	0.377	indeterminate
SaProt	LLR -12.99	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.7	GERP 2.6, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 27 kb · p 1.2e-24 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R125Q vs ClinVar R152Q) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0022% South Asian · 2/91,014 alleles

Filtering AF 0.000365% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000137%

Overall 0.000342% 5/1,461,208 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0022%	45,507
European (non-Finnish)	0.000254%	393,199

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: CELF1
Protein: p.Arg152Gln
Coding: c.455G>A
MANE Select: NM_001376376
dbSNP: rs776176922
Type: single nucleotide variant
Location: chr11:47484460 (GRCh38)
Gene constraint: LOEUF 0.247 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.17 · 8 PDB
Residue 152: the rrm 2 domain; a β-strand

Full CELF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CELF1 p.Ser507= Benign ★★ same type
CELF1 c.606+2T>A Uncertain significance ★ same type
CELF1 p.Ala237Thr Uncertain significance ★ ⚠ same type
CELF1 p.Ala401Val Uncertain significance ★ ⚠ same type
CELF1 p.Ala99Val Uncertain significance ★ ⚠ same type
CELF1 p.Arg506His Uncertain significance ★ ⚠ same type
CELF1 p.Arg60Gln Uncertain significance ★ ⚠ same type
CELF1 p.Arg96His 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/celf1-p-arg152gln (accessed [today's date]).

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