EP400 p.Arg705Gln
c.2114G>A · VCV4018370
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00271%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.315 | indeterminate |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 8.5 | GERP 0.5, phastCons 1 |
| Regional constraint | o/e 0.95 | unconstrained · MANE · 45 kb · p 0.17 · regional, not allelic |
| Overall | ||
| CADD | 23.8 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00271%
European (non-Finnish) · 32/1,180,032 alleles
Filtering AF
0.00196%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00168%
Overall
0.00217%
35/1,613,958 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00271% | 36,876 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,482 |
| African / African-American | 0.00134% | 74,884 |
| South Asian | 0.0011% | 91,084 |
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
- EP400
- Protein
- p.Arg705Gln
- Coding
- c.2114G>A
- MANE Select
- NM_015409
- Type
- single nucleotide variant
- Location
- chr12:131986698 (GRCh38)
- Gene constraint
- LOEUF 0.365 · pLI 1.00 (gnomAD)
- Residue 705
- the 'disordered' region
Similar variants
- EP400 p.Arg705fs Uncertain significance ★ same residue
- EP400 p.Thr664Ala Uncertain significance ★★ same type
- EP400 c.1435+8G>A Benign ★★ same type
- EP400 c.7027-9C>T Benign ★★ same type
- EP400 p.Ala146= Likely benign ★★ same type
- EP400 p.Ala1649Thr Benign/Likely benign ★★ same type
- EP400 p.Ala1764= Benign ★★ same type
- EP400 p.Ala244= Likely benign ★★ 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/ep400-p-arg705gln (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown