Is CREBBP p.Ser807Thr (c.2420G>C) pathogenic?

CREBBP p.Ser807Thr (c.2420G>C) is classified Conflicting classifications of pathogenicity in CREBBP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2024-05-23). AlphaMissense: likely benign (0.0764); Very rare (popmax 0.004%, afr); Associated with Menke-Hennekam syndrome 1.

What condition is associated with CREBBP p.Ser807Thr (c.2420G>C)?

CREBBP p.Ser807Thr (c.2420G>C) is associated with Menke-Hennekam syndrome 1, Rubinstein-Taybi syndrome due to CREBBP mutations, Rubinstein-Taybi syndrome (ClinVar).

How common is CREBBP p.Ser807Thr (c.2420G>C) in the general population?

CREBBP p.Ser807Thr (c.2420G>C) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CREBBP p.Ser807Thr (c.2420G>C)?

AlphaMissense predicts likely benign (score 0.0764) — an in-silico prediction, not a clinical call.

CREBBP p.Ser807Thr

c.2420G>C · rs750178517 · VCV931917

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0764 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Menke-Hennekam syndrome 1

Computational evidence

Protein change
AlphaMissense	0.0764	likely benign
REVEL	0.207	benign-leaning
SaProt	LLR -7.13	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.01	GERP 0.77, phastCons 0.012
Regional constraint	o/e 1.03	unconstrained · MANE · 19 kb · p 0.52 · regional, not allelic
Overall
CADD	20.7	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

Grpmax group 0.004% African / African-American · 3/74,936 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000248% 4/1,613,606 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,979
South Asian	0.0011%	91,060

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.Ser807Thr
Coding: c.2420G>C
MANE Select: NM_004380
dbSNP: rs750178517
Type: single nucleotide variant
Location: chr16:3773794 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 807: the 'disordered' region

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

Disease context

Menke-Hennekam syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Rubinstein-Taybi syndrome due to CREBBP mutations Rubinstein-Taybi syndrome

Similar variants

CREBBP p.Ser807Asn Likely benign ★ 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-ser807thr (accessed [today's date]).

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