Is CREBBP p.Val1818= (c.5454G>A) pathogenic?

CREBBP p.Val1818= (c.5454G>A) is classified Benign in CREBBP (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-06-01). Low-frequency (popmax 1.12%, nfe); Associated with Rubinstein-Taybi syndrome.

What condition is associated with CREBBP p.Val1818= (c.5454G>A)?

CREBBP p.Val1818= (c.5454G>A) is associated with Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Val1818= (c.5454G>A) in the general population?

CREBBP p.Val1818= (c.5454G>A) is low-frequency (popmax 1.12%, nfe) (gnomAD).

CREBBP p.Val1818=

c.5454G>A · rs61754523 · VCV158386

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

low-frequency (popmax 1.12%, nfe)

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 -0.76	GERP -3.8, phastCons 0.005
Overall
CADD	3.757	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.12% European (non-Finnish) · 13,179/1,180,024 alleles

Filtering AF 1.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.09%

Overall 0.943% 15,228/1,614,204 alleles · low-frequency

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	1.72%	58
European (non-Finnish)grpmax	1.12%	90
Amishnot grpmax-eligible	1.1%	91
Remaining individualsnot grpmax-eligible	0.746%	134
Admixed American	0.315%	318
African / African-American	0.171%	586
South Asian	0.132%	759
Ashkenazi Jewishnot grpmax-eligible	0.105%	955
Middle Eastern	0.099%	1,010

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val1818=
Coding: c.5454G>A
MANE Select: NM_004380
dbSNP: rs61754523
Type: single nucleotide variant
Location: chr16:3729593 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 1818: the 'interaction with trerf1' region; an α-helix

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 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
CREBBP p.Arg1867Gln 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-val1818 (accessed [today's date]).

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