Is CREBBP p.Ser1684= (c.5052C>T) pathogenic?

CREBBP p.Ser1684= (c.5052C>T) is classified Benign in CREBBP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-28). Common (popmax 11.1%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Inborn genetic diseases.

What condition is associated with CREBBP p.Ser1684= (c.5052C>T)?

CREBBP p.Ser1684= (c.5052C>T) is associated with Inborn genetic diseases, Rubinstein-Taybi syndrome (ClinVar).

CREBBP p.Ser1684=

Q: How common is CREBBP p.Ser1684= (c.5052C>T) in the general population?

CREBBP p.Ser1684= (c.5052C>T) is common (popmax 11.1%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.5052C>T · rs2072381 · VCV95052

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 11.1%, eas) — too common for a highly-penetrant pathogenic allele

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 1.9	GERP 0.91, phastCons 1
Overall
CADD	9.904	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.1% East Asian · 4,974/44,870 alleles

Filtering AF 10.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.7%

Overall 0.358% 5,780/1,614,162 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	11.1%	9
Remaining individualsnot grpmax-eligible	0.466%	215
South Asian	0.278%	360
Middle Eastern	0.132%	758
Admixed American	0.025%	4,001
European (non-Finnish)	0.0191%	5,245
Finnishnot grpmax-eligible	0.0172%	5,821
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,869

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.Ser1684=
Coding: c.5052C>T
MANE Select: NM_004380
dbSNP: rs2072381
Type: single nucleotide variant
Location: chr16:3731312 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 1684: the 'interaction with trerf1' region; the cbp/p300-type hat domain

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

Similar variants

CREBBP p.Ser1684Tyr Uncertain significance ★ ⚠ same residue
CREBBP p.Ser1684Pro Likely pathogenic ★ 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

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-ser1684 (accessed [today's date]).

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