NARS2 p.Pro18=
c.54C>T · rs745763966 · VCV2183063
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.005%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP 0.22 | GERP -4.1, phastCons 0.36 |
| Overall | ||
| CADD | 4.632 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.005%
Admixed American · 3/60,012 alleles
Filtering AF
0.00133%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000668%
Overall
0.000743%
12/1,614,050 alleles · very rare
exomes 11/1,461,828 · genomes 1/152,222 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.005% | 20,004 |
| Remaining individualsnot grpmax-eligible | 0.0016% | 62,480 |
| European (non-Finnish) | 0.000678% | 147,505 |
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
- NARS2
- Protein
- p.Pro18=
- Coding
- c.54C>T
- MANE Select
- NM_024678
- dbSNP
- rs745763966
- Type
- single nucleotide variant
- Location
- chr11:78574435 (GRCh38)
- Gene constraint
- LOEUF 1.253 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 91.59
Similar variants
- NARS2 p.Pro18Leu Uncertain significance ★ ⚠ same residue
- NARS2 p.Pro18Ser Uncertain significance ★ ⚠ same residue
- NARS2 p.Arg140Ter Pathogenic ★★ same type
- NARS2 p.Arg243Ter Pathogenic/Likely pathogenic ★★ same type
- NARS2 p.Asn317= Pathogenic/Likely pathogenic ★★ same type
- NARS2 p.Tyr323Ter Pathogenic/Likely pathogenic ★★ same type
- NARS2 p.Tyr412Ter Pathogenic ★★ same type
- NARS2 c.689+6A>G 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/nars2-p-pro18 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown