NIN p.Pro1971=
c.5913G>A · rs145555295 · VCV722407
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
ultra-rare (popmax 0.0539%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.008 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -8.4 | GERP -3.1 |
| Overall | ||
| CADD | 0.408 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0539%
European (non-Finnish) · 636/1,178,876 alleles
Filtering AF
0.0505%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.049%
Overall
0.0462%
744/1,611,808 alleles · ultra-rare
exomes 685/1,459,502 · genomes 59/152,306 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0539% | 1,854 |
| Admixed American | 0.0518% | 1,930 |
| Remaining individualsnot grpmax-eligible | 0.0497% | 2,013 |
| African / African-American | 0.036% | 2,778 |
| Middle Eastern | 0.0351% | 2,853 |
| East Asian | 0.0245% | 4,076 |
| South Asian | 0.00551% | 18,155 |
| Finnishnot grpmax-eligible | 0.00156% | 63,974 |
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
- NIN
- Protein
- p.Pro1971=
- Coding
- c.5913G>A
- MANE Select
- NM_020921
- dbSNP
- rs145555295
- Type
- single nucleotide variant
- Location
- chr14:50729688 (GRCh38)
- Gene constraint
- LOEUF 0.62 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 64.47
Similar variants
- NIN p.Pro1971Gln Conflicting classifications of pathogenicity ★ ⚠ same residue
- NIN p.Pro1971Leu Uncertain significance ★ ⚠ same residue
- NIN p.Arg2039Ter Likely pathogenic ★★ same type
- NIN p.Ala1049Thr Uncertain significance ★★ ⚠ same type
- NIN p.Ala1212Val Uncertain significance ★★ ⚠ same type
- NIN p.Ala1350Gly Uncertain significance ★★ ⚠ same type
- NIN p.Ala1741Val Uncertain significance ★★ ⚠ same type
- NIN p.Ala1755Thr 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/nin-p-pro1971 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown