Is CREBBP p.Pro852Gln (c.2555C>A) pathogenic?

CREBBP p.Pro852Gln (c.2555C>A) is classified Uncertain significance in CREBBP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-09-11). AlphaMissense: likely benign (0.1131); Absent from gnomAD v4.1; Associated with CREBBP-related disorder.

What condition is associated with CREBBP p.Pro852Gln (c.2555C>A)?

CREBBP p.Pro852Gln (c.2555C>A) is associated with CREBBP-related disorder (ClinVar).

How common is CREBBP p.Pro852Gln (c.2555C>A) in the general population?

CREBBP p.Pro852Gln (c.2555C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CREBBP p.Pro852Gln (c.2555C>A)?

AlphaMissense predicts likely benign (score 0.1131) — an in-silico prediction, not a clinical call.

CREBBP p.Pro852Gln

c.2555C>A · VCV3347877

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1131 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

CREBBP-related disorder

Computational evidence

Protein change
AlphaMissense	0.1131	likely benign
REVEL	0.469	indeterminate
SaProt	LLR -6.13	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 9.9	GERP 1.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 19 kb · p 0.52 · regional, not allelic
Overall
CADD	24.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CREBBP
Protein: p.Pro852Gln
Coding: c.2555C>A
MANE Select: NM_004380
Type: single nucleotide variant
Location: chr16:3770895 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 852: the 'disordered' region

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

Disease context

CREBBP-related disorder

Similar variants

CREBBP p.Pro852Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
CREBBP p.Pro852= Likely benign ★ same residue
CREBBP c.1823+5G>A Pathogenic/Likely pathogenic ★★ same condition
CREBBP c.3779+1G>T Pathogenic ★★ same condition
CREBBP p.Arg1378Pro Pathogenic/Likely pathogenic ★★ ⚠ same condition
CREBBP p.Arg1392Ter Pathogenic ★★ same condition
CREBBP p.Arg1867Trp Pathogenic/Likely pathogenic ★★ same condition
CREBBP p.Arg1868Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition

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-pro852gln (accessed [today's date]).

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