Is EP300 p.Met1965fs (c.5894dup) pathogenic?

EP300 p.Met1965fs (c.5894dup) is classified Likely pathogenic in EP300 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-04). Absent from gnomAD; Associated with Rubinstein-Taybi syndrome due to EP300 haploinsufficiency.

How common is EP300 p.Met1965fs (c.5894dup) in the general population?

EP300 p.Met1965fs (c.5894dup) is absent from gnomAD (gnomAD).

EP300 p.Met1965fs

Q: What condition is associated with EP300 p.Met1965fs (c.5894dup)?

EP300 p.Met1965fs (c.5894dup) is associated with Rubinstein-Taybi syndrome due to EP300 haploinsufficiency, Rubinstein-Taybi syndrome (ClinVar).

c.5894dup · rs2517833590 · VCV1809810

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

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	escapes	premature termination codon in the last exon (31 of 31) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 3.1	GERP 1.4, phastCons 0.97

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.Met1965fs
Coding: c.5894dup
MANE Select: NM_001429
dbSNP: rs2517833590
Type: Duplication
Location: chr22:41177604 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB

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

Also linked: Rubinstein-Taybi syndrome

Similar variants

EP300 p.Asn1236fs Pathogenic ★★ same condition
EP300 p.Asn779fs Pathogenic ★★ same condition
EP300 p.Pro1961fs Pathogenic/Likely pathogenic ★★ same condition
EP300 p.Val2036fs Pathogenic/Likely pathogenic ★★ same condition
EP300 p.Asn2357_Ala2365dup Uncertain significance ★★ same condition
EP300 p.Gln2153_Leu2154insProGlnGlnGln Uncertain significance ★★ same condition
EP300 p.Gln2155_Pro2156insGlnGlnLeuGln Uncertain significance ★★ same condition
EP300 c.1283-19dup Benign/Likely benign ★★ 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-met1965fs (accessed [today's date]).

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