EP400 p.Pro141Leu
c.422C>T · rs769410643 · VCV3089311
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00796%, sas)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.644 | pathogenic-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 7.4 | phastCons 0.98 |
| Regional constraint | o/e 0.71 | unconstrained · MANE · 549 bp · p 5.4e-06 · regional, not allelic |
| Overall | ||
| CADD | 23.2 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00796%
South Asian · 7/87,968 alleles
Filtering AF
0.0037%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00262%
Overall
0.00215%
34/1,583,938 alleles · very rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.00796% | 12,567 |
| Admixed American | 0.00362% | 27,594 |
| Remaining individualsnot grpmax-eligible | 0.00327% | 30,617 |
| African / African-American | 0.0027% | 37,095 |
| East Asian | 0.00233% | 42,932 |
| European (non-Finnish) | 0.00172% | 58,266 |
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.Pro141Leu
- Coding
- c.422C>T
- MANE Select
- NM_015409
- dbSNP
- rs769410643
- Type
- single nucleotide variant
- Location
- chr12:131961041 (GRCh38)
- Gene constraint
- LOEUF 0.365 · pLI 1.00 (gnomAD)
- Residue 141
- the 'disordered' region
Similar variants
- 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
- EP400 p.Ala2803= 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-pro141leu (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown