Is CREBBP p.Val2002= (c.6006G>T) pathogenic?

CREBBP p.Val2002= (c.6006G>T) is classified Conflicting classifications of pathogenicity in CREBBP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-10-26). Very rare (popmax 0.00536%, afr); Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Val2002= (c.6006G>T)?

CREBBP p.Val2002= (c.6006G>T) is associated with Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Val2002= (c.6006G>T) in the general population?

CREBBP p.Val2002= (c.6006G>T) is very rare (popmax 0.00536%, afr) (gnomAD).

CREBBP p.Val2002=

c.6006G>T · rs768100377 · VCV595866

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00536%, afr)

Conditions

Rubinstein-Taybi syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.051	GERP -0.36, phastCons 0.82
Overall
CADD	1.4	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00536% African / African-American · 4/74,684 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000944% 15/1,588,220 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00536%	18,671
Remaining individualsnot grpmax-eligible	0.00324%	30,856
European (non-Finnish)	0.000767%	130,320

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: CREBBP
Protein: p.Val2002=
Coding: c.6006G>T
MANE Select: NM_004380
dbSNP: rs768100377
Type: single nucleotide variant
Location: chr16:3729041 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 2002: the 'disordered' region

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

Disease context

Rubinstein-Taybi syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CREBBP p.Val2002Ala Uncertain significance ⚠ same residue
CREBBP c.2881-13G>A Pathogenic/Likely pathogenic ★★ same condition
CREBBP c.3779+1G>A Pathogenic ★★ same condition
CREBBP c.3779+1G>T Pathogenic ★★ same condition
CREBBP c.3836+1G>A Pathogenic ★★ same condition
CREBBP p.Arg1103Ter Pathogenic ★★ same condition
CREBBP p.Arg1233Lys Pathogenic/Likely pathogenic ★★ ⚠ same condition
CREBBP p.Arg1498Ter 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-val2002 (accessed [today's date]).

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