Is CREBBP p.Phe276Ser (c.827T>C) pathogenic?

CREBBP p.Phe276Ser (c.827T>C) is classified Uncertain significance in CREBBP (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-18). AlphaMissense: likely pathogenic (0.7527); Absent from gnomAD v4.1; Associated with CREBBP-related disorder.

What condition is associated with CREBBP p.Phe276Ser (c.827T>C)?

CREBBP p.Phe276Ser (c.827T>C) is associated with CREBBP-related disorder (ClinVar).

How common is CREBBP p.Phe276Ser (c.827T>C) in the general population?

CREBBP p.Phe276Ser (c.827T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CREBBP p.Phe276Ser (c.827T>C)?

AlphaMissense predicts likely pathogenic (score 0.7527) — an in-silico prediction, not a clinical call.

CREBBP p.Phe276Ser

c.827T>C · rs2053922967 · VCV2631698

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7527 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CREBBP-related disorder

Computational evidence

Protein change
AlphaMissense	0.7527	likely pathogenic
REVEL	0.681	pathogenic-leaning
SaProt	LLR -5.15	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.73	unconstrained · MANE · 17 kb · p 0.00046 · regional, not allelic
Overall
CADD	24.6	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CREBBP
Protein: p.Phe276Ser
Coding: c.827T>C
MANE Select: NM_004380
dbSNP: rs2053922967
Type: single nucleotide variant
Location: chr16:3810751 (GRCh38)
Gene constraint: LOEUF 0.101 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.31 · 144 PDB
Residue 276: the 'interaction with srcap' region; the 'disordered' region

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

Disease context

CREBBP-related disorder

Similar variants

CREBBP c.1823+5G>A Pathogenic/Likely pathogenic ★★ same condition
CREBBP c.3779+1G>T Pathogenic ★★ same condition
CREBBP p.Arg1378Pro Pathogenic/Likely pathogenic ★★ ⚠ same condition
CREBBP p.Arg1392Ter Pathogenic ★★ same condition
CREBBP p.Arg1867Trp Pathogenic/Likely pathogenic ★★ same condition
CREBBP p.Arg1868Gln Pathogenic/Likely pathogenic ★★ ⚠ same condition
CREBBP p.Arg75Ter Pathogenic ★★ same condition
CREBBP p.Asp1480Gly 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-phe276ser (accessed [today's date]).

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