Is CREB1 p.Gln30Arg (c.89A>G) pathogenic?

CREB1 p.Gln30Arg (c.89A>G) is classified Uncertain significance in CREB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). AlphaMissense: likely benign (0.1625); Very rare (popmax 6.84e-05%).

How common is CREB1 p.Gln30Arg (c.89A>G) in the general population?

CREB1 p.Gln30Arg (c.89A>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about CREB1 p.Gln30Arg (c.89A>G)?

AlphaMissense predicts likely benign (score 0.1625) — an in-silico prediction, not a clinical call.

CREB1 p.Gln30Arg

c.89A>G · rs1327500450 · VCV2545123

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1625 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1625	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -10.10	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.8, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,617 bp · p 0.59 · regional, not allelic
Overall
CADD	23.5	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 6.84e-05%

Overall 6.84e-05% 1/1,460,996 alleles · very rare

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: CREB1
Protein: p.Gln30Arg
Coding: c.89A>G
MANE Select: NM_004379
dbSNP: rs1327500450
Type: single nucleotide variant
Location: chr2:207555724 (GRCh38)
Gene constraint: LOEUF 0.189 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 62.38 · 4 PDB

Full CREB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CREB1 p.Ala72= Benign ★★ same type
CREB1 p.Thr194= Benign/Likely benign ★★ same type
CREB1 p.Ala148Thr Uncertain significance ★ ⚠ same type
CREB1 p.Ala150Ser Uncertain significance ★ ⚠ same type
CREB1 p.Ala176Glu Uncertain significance ★ ⚠ same type
CREB1 p.Ala259Thr Uncertain significance ★ ⚠ same type
CREB1 p.Ala43Glu Uncertain significance ★ ⚠ same type
CREB1 p.Ala46Gly 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/creb1-p-gln30arg (accessed [today's date]).

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