Is CREBBP p.Ser2065= (c.6195C>T) pathogenic?

CREBBP p.Ser2065= (c.6195C>T) is classified Benign/Likely benign in CREBBP (ClinVar, Multiple submitters, 6 submitters; last evaluated 2025-12-15). Ultra-rare (popmax 0.0869%, eas); Associated with Inborn genetic diseases.

What condition is associated with CREBBP p.Ser2065= (c.6195C>T)?

CREBBP p.Ser2065= (c.6195C>T) is associated with Inborn genetic diseases, Rubinstein-Taybi syndrome due to CREBBP mutations, Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Ser2065= (c.6195C>T) in the general population?

CREBBP p.Ser2065= (c.6195C>T) is ultra-rare (popmax 0.0869%, eas) (gnomAD).

CREBBP p.Ser2065=

c.6195C>T · rs374150949 · VCV587874

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0869%, eas)

Conditions

Inborn genetic diseases

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 -1.1	GERP -3.2
Overall
CADD	4.29	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0869% East Asian · 39/44,872 alleles

Filtering AF 0.0653% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.00756% 122/1,613,154 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0869%	1,151
Remaining individualsnot grpmax-eligible	0.04%	2,499
South Asian	0.0285%	3,503
Admixed American	0.00333%	30,018
African / African-American	0.00266%	37,526
European (non-Finnish)	0.00237%	42,141

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.Ser2065=
Coding: c.6195C>T
MANE Select: NM_004380
dbSNP: rs374150949
Type: single nucleotide variant
Location: chr16:3728852 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 2065: a turn

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Rubinstein-Taybi syndrome due to CREBBP mutations Rubinstein-Taybi syndrome Menke-Hennekam syndrome 1

Similar variants

CREBBP p.Ser2065Arg Uncertain significance ★★ ⚠ same residue
CREBBP c.2881-13G>A Pathogenic/Likely pathogenic ★★ same condition
CREBBP c.3369+1G>T 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 c.3914+3G>T Likely pathogenic ★★ same condition
CREBBP c.3982+1G>A 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-ser2065 (accessed [today's date]).

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