Is CREBBP p.Ala1870Pro (c.5608G>C) pathogenic?

CREBBP p.Ala1870Pro (c.5608G>C) is classified Likely pathogenic in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-07). AlphaMissense: likely pathogenic (0.9974); Absent from gnomAD v4.1; Associated with CREBBP-related disorder.

What condition is associated with CREBBP p.Ala1870Pro (c.5608G>C)?

CREBBP p.Ala1870Pro (c.5608G>C) is associated with CREBBP-related disorder (ClinVar).

How common is CREBBP p.Ala1870Pro (c.5608G>C) in the general population?

CREBBP p.Ala1870Pro (c.5608G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CREBBP p.Ala1870Pro (c.5608G>C)?

AlphaMissense predicts likely pathogenic (score 0.9974) — an in-silico prediction, not a clinical call.

CREBBP p.Ala1870Pro

c.5608G>C · rs1411086593 · VCV2637055

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9974 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CREBBP-related disorder

Computational evidence

Protein change
AlphaMissense	0.9974	likely pathogenic ✓ concordant with ClinVar · top 9% in CREBBP
REVEL	0.699	pathogenic-leaning
SaProt	LLR -8.32	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.36	unconstrained · MANE · 305 bp · p 1.2e-14 · regional, not allelic
Overall
CADD	23.7	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

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.Ala1870Pro
Coding: c.5608G>C
MANE Select: NM_004380
dbSNP: rs1411086593
Type: single nucleotide variant
Location: chr16:3729439 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 1870: a UniProt-annotated variant site (in mkhk1); the 'interaction with trerf1' region

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

Disease context

CREBBP-related disorder

Similar variants

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
CREBBP p.Arg75Ter Pathogenic ★★ same condition
CREBBP p.Asp1480Gly 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-ala1870pro (accessed [today's date]).

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