Is CREBBP p.Ser893Trp (c.2678C>G) pathogenic?

CREBBP p.Ser893Trp (c.2678C>G) is classified Uncertain significance in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-21). AlphaMissense: ambiguous (0.3683); Very rare (popmax 0.00134%, afr).

How common is CREBBP p.Ser893Trp (c.2678C>G) in the general population?

CREBBP p.Ser893Trp (c.2678C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CREBBP p.Ser893Trp (c.2678C>G)?

AlphaMissense predicts ambiguous (score 0.3683) — an in-silico prediction, not a clinical call.

CREBBP p.Ser893Trp

c.2678C>G · rs142047649 · VCV2506841

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3683 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
AlphaMissense	0.3683	ambiguous
REVEL	0.627	indeterminate
SaProt	LLR -10.92	damaging
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 19 kb · p 0.52 · regional, not allelic
Overall
CADD	27.1	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 0.00134% African / African-American · 1/74,894 alleles

Overall 0.000658% 1/152,086 alleles · very rare

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.Ser893Trp
Coding: c.2678C>G
MANE Select: NM_004380
dbSNP: rs142047649
Type: single nucleotide variant
Location: chr16:3770772 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 893: the 'disordered' region

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

Similar variants

CREBBP p.Ser893Leu Benign/Likely benign ★★ same residue
CREBBP p.Ser893Ter Likely pathogenic ★ same residue
CREBBP p.Ser893= Conflicting classifications of pathogenicity ★ same residue
CREBBP c.1823+5G>A Pathogenic/Likely pathogenic ★★ same type
CREBBP c.2881-13G>A Pathogenic/Likely pathogenic ★★ same type
CREBBP c.3369+1G>T Pathogenic/Likely pathogenic ★★ same type
CREBBP c.3779+1G>A Pathogenic ★★ same type
CREBBP c.3779+1G>T Pathogenic ★★ same type

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-ser893trp (accessed [today's date]).

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