Is EP300 p.Gln72Lys (c.214C>A) pathogenic?

EP300 p.Gln72Lys (c.214C>A) is classified Likely benign in EP300 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2023-07-20). AlphaMissense: likely benign (0.2124); Very rare (popmax 0.00517%, nfe); Associated with Inborn genetic diseases.

What condition is associated with EP300 p.Gln72Lys (c.214C>A)?

EP300 p.Gln72Lys (c.214C>A) is associated with Inborn genetic diseases, Rubinstein-Taybi syndrome due to EP300 haploinsufficiency, autosomal dominant cerebellar ataxia (ClinVar).

How common is EP300 p.Gln72Lys (c.214C>A) in the general population?

EP300 p.Gln72Lys (c.214C>A) is very rare (popmax 0.00517%, nfe) (gnomAD).

What do computational predictors say about EP300 p.Gln72Lys (c.214C>A)?

AlphaMissense predicts likely benign (score 0.2124) — an in-silico prediction, not a clinical call.

EP300 p.Gln72Lys

c.214C>A · rs539635560 · VCV1298318

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2124 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00517%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2124	likely benign
REVEL	0.509	indeterminate
SaProt	LLR -7.30	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	Δ0.20	donor gain · deltas
Pangolin	Δ0.29	gain · loss 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 35 kb · p 0.42 · regional, not allelic
Overall
CADD	25.5	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 0.00517% European (non-Finnish) · 61/1,180,044 alleles

Filtering AF 0.0041% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00372%

Overall 0.0039% 63/1,614,042 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00517%	19,345
Remaining individualsnot grpmax-eligible	0.0016%	62,484
Finnishnot grpmax-eligible	0.00156%	64,026

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: EP300
Protein: p.Gln72Lys
Coding: c.214C>A
MANE Select: NM_001429
dbSNP: rs539635560
Type: single nucleotide variant
Location: chr22:41117306 (GRCh38)
Gene constraint: LOEUF 0.164 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 54.88 · 60 PDB
Residue 72: the 'interaction with alx1' region; the 'interaction with rora' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Rubinstein-Taybi syndrome due to EP300 haploinsufficiency autosomal dominant cerebellar ataxia

Similar variants

EP300 c.1282+1G>A Pathogenic/Likely pathogenic ★★ same condition
EP300 c.3671+1G>A Pathogenic/Likely pathogenic ★★ same condition
EP300 c.3729-2A>G Pathogenic/Likely pathogenic ★★ same condition
EP300 c.3857A>G Pathogenic/Likely pathogenic ★★ ⚠ same condition
EP300 p.Arg1055Ter Pathogenic ★★ same condition
EP300 p.Arg1312Ter Pathogenic ★★ same condition
EP300 p.Arg1356Ter Pathogenic ★★ same condition
EP300 p.Arg1462Ter 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/ep300-p-gln72lys (accessed [today's date]).

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