EPRS1 p.Pro696=
c.2088G>A · rs145416177 · VCV1680972
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0165%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -13 | GERP -4.9 |
| Overall | ||
| CADD | 0.164 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0165%
Middle Eastern · 1/6,062 alleles
Filtering AF
0.00845%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00661%
Overall
0.0067%
108/1,612,552 alleles · ultra-rare
exomes 97/1,460,362 · genomes 11/152,190 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0165% | 6,062 |
| South Asian | 0.0143% | 7,003 |
| Remaining individualsnot grpmax-eligible | 0.00961% | 10,407 |
| African / African-American | 0.00934% | 10,709 |
| Admixed American | 0.00667% | 14,998 |
| European (non-Finnish) | 0.00653% | 15,307 |
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
- EPRS1
- Protein
- p.Pro696=
- Coding
- c.2088G>A
- MANE Select
- NM_004446
- dbSNP
- rs145416177
- Type
- single nucleotide variant
- Location
- chr1:220001231 (GRCh38)
- Gene constraint
- LOEUF 0.549 · pLI 0.02 (gnomAD)
- Structure
- AlphaFold pLDDT 83.55 · 33 PDB
- Residue 696
- the 'glutamate--trna ligase' region; a UniProt-annotated variant site (in hld15)
Similar variants
- EPRS1 p.Arg1278Ter Pathogenic/Likely pathogenic ★★ same type
- EPRS1 p.Gln985Ter Pathogenic ★★ same type
- EPRS1 c.4244+3A>C Uncertain significance ★★ same type
- EPRS1 p.Ala1183Val Uncertain significance ★★ ⚠ same type
- EPRS1 p.Ala174Thr Uncertain significance ★★ ⚠ same type
- EPRS1 p.Ala301Thr Uncertain significance ★★ ⚠ same type
- EPRS1 p.Ala901Val Uncertain significance ★★ ⚠ same type
- EPRS1 p.Arg1050Cys Uncertain significance ★★ ⚠ 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/eprs1-p-pro696 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown