Is CREBBP p.Gln1908Arg (c.5723A>G) pathogenic?

CREBBP p.Gln1908Arg (c.5723A>G) is classified Uncertain significance in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-13). AlphaMissense: likely benign (0.3023); Absent from gnomAD v4.1.

How common is CREBBP p.Gln1908Arg (c.5723A>G) in the general population?

CREBBP p.Gln1908Arg (c.5723A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CREBBP p.Gln1908Arg (c.5723A>G)?

AlphaMissense predicts likely benign (score 0.3023) — an in-silico prediction, not a clinical call.

CREBBP p.Gln1908Arg

c.5723A>G · VCV3777373

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3023 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,563,990)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3023	likely benign
REVEL	0.365	indeterminate
SaProt	LLR -7.58	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 568 bp · p 0.93 · regional, not allelic
Overall
CADD	23.3	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 and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,563,990). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CREBBP
Protein: p.Gln1908Arg
Coding: c.5723A>G
MANE Select: NM_004380
Type: single nucleotide variant
Location: chr16:3729324 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 1908: the 'disordered' region

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

Similar variants

CREBBP p.Gln1908fs Pathogenic same residue
CREBBP c.1823+5G>A Pathogenic/Likely pathogenic ★★ same type
CREBBP c.2881-13G>A Pathogenic/Likely pathogenic ★★ same type
CREBBP c.3369+1G>T Pathogenic/Likely pathogenic ★★ same type
CREBBP c.3779+1G>A Pathogenic ★★ same type
CREBBP c.3779+1G>T Pathogenic ★★ same type
CREBBP c.3836+1G>A Pathogenic ★★ same type
CREBBP c.3914+3G>T Likely pathogenic ★★ 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/crebbp-p-gln1908arg (accessed [today's date]).

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