Is EP300 p.Met1124fs (c.3367del) pathogenic?

EP300 p.Met1124fs (c.3367del) is classified Pathogenic in EP300 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-05). Absent from gnomAD; Associated with Rubinstein-Taybi syndrome due to EP300 haploinsufficiency.

What condition is associated with EP300 p.Met1124fs (c.3367del)?

EP300 p.Met1124fs (c.3367del) is associated with Rubinstein-Taybi syndrome due to EP300 haploinsufficiency (ClinVar).

How common is EP300 p.Met1124fs (c.3367del) in the general population?

EP300 p.Met1124fs (c.3367del) is absent from gnomAD (gnomAD).

EP300 p.Met1124fs

c.3367del · rs1601624722 · VCV827624

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 18 of 31
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 8.7	GERP 2.3, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: EP300
Protein: p.Met1124fs
Coding: c.3367del
MANE Select: NM_001429
dbSNP: rs1601624722
Type: Deletion
Location: chr22:41157274 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 1124: an α-helix; the bromo domain

Full EP300 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Rubinstein-Taybi syndrome due to EP300 haploinsufficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EP300 p.Asn2305fs Pathogenic/Likely pathogenic ★★ same condition
EP300 p.Ile1457_Lys1459delinsMet Pathogenic/Likely pathogenic ★★ same condition
EP300 p.Ile2100fs Pathogenic/Likely pathogenic ★★ same condition
EP300 p.Lys1228fs Pathogenic ★★ same condition
EP300 p.Pro742fs Pathogenic ★★ same condition
EP300 p.Ser457fs Pathogenic ★★ same condition
EP300 p.Ala1853_Pro1855del Uncertain significance ★★ same condition
EP300 p.Arg1645_Ala1647delinsPro Uncertain significance ★★ 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/ep300-p-met1124fs (accessed [today's date]).

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