PNN p.Arg185=
c.553A>C · rs141299673 · VCV788117
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
rare (popmax 0.337%, nfe)
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 6.7 | GERP 0.49, phastCons 1 |
| Overall | ||
| CADD | 12.97 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.337%
European (non-Finnish) · 3,982/1,179,984 alleles
Filtering AF
0.329%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.325%
Overall
0.276%
4,459/1,614,062 alleles · rare
exomes 4,212/1,461,696 · genomes 247/152,366 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.337% | 296 |
| South Asian | 0.284% | 353 |
| Remaining individualsnot grpmax-eligible | 0.163% | 613 |
| Finnishnot grpmax-eligible | 0.0703% | 1,423 |
| African / African-American | 0.0546% | 1,831 |
| Middle Eastern | 0.0495% | 2,021 |
| Admixed American | 0.0433% | 2,308 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00676% | 14,803 |
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
- PNN
- Protein
- p.Arg185=
- Coding
- c.553A>C
- MANE Select
- NM_002687
- dbSNP
- rs141299673
- Type
- single nucleotide variant
- Location
- chr14:39179145 (GRCh38)
- Gene constraint
- LOEUF 0.564 · pLI 0.43 (gnomAD)
- Structure
- AlphaFold pLDDT 58.30
- Residue 185
- the 'necessary for interaction with rnps1' region
Similar variants
- PNN c.185+10C>T Benign ★★ same type
- PNN p.Glu526Lys Benign ★★ same type
- PNN p.Ser624= Benign ★★ same type
- PNN p.Ala111Thr Uncertain significance ★ ⚠ same type
- PNN p.Ala343Val Uncertain significance ★ ⚠ same type
- PNN p.Ala421Pro Uncertain significance ★ ⚠ same type
- PNN p.Ala421Val Uncertain significance ★ ⚠ same type
- PNN p.Ala474Val 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/pnn-p-arg185 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown