Is CREBBP p.Pro2005Arg (c.6014C>G) pathogenic?

CREBBP p.Pro2005Arg (c.6014C>G) is classified Uncertain significance in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-20). AlphaMissense: ambiguous (0.3545); Absent from gnomAD v4.1.

How common is CREBBP p.Pro2005Arg (c.6014C>G) in the general population?

CREBBP p.Pro2005Arg (c.6014C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CREBBP p.Pro2005Arg (c.6014C>G)?

AlphaMissense predicts ambiguous (score 0.3545) — an in-silico prediction, not a clinical call.

CREBBP p.Pro2005Arg

c.6014C>G · rs2151306708 · VCV2502788

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3545 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3545	ambiguous
REVEL	0.39	indeterminate
SaProt	LLR -10.48	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP -0.28, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 568 bp · p 0.93 · regional, not allelic
Overall
CADD	24.1	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.Pro2005Arg
Coding: c.6014C>G
MANE Select: NM_004380
dbSNP: rs2151306708
Type: single nucleotide variant
Location: chr16:3729033 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 2005: the 'disordered' region

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

Similar variants

CREBBP p.Pro2005Thr Uncertain significance ★ ⚠ same residue
CREBBP p.Pro2005Ser Likely benign ★ 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

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-pro2005arg (accessed [today's date]).

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