NAAA p.Ile80=
c.240C>T · rs192282293 · VCV717150
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
low-frequency (popmax 1.34%, 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 -1.4 | GERP -3.1 |
| Overall | ||
| CADD | 2.48 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
1.34%
Middle Eastern · 81/6,062 alleles
Filtering AF
1.1%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.02%
Overall
0.11%
1,782/1,614,080 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 1.34% | 75 |
| Ashkenazi Jewishnot grpmax-eligible | 0.605% | 165 |
| Remaining individualsnot grpmax-eligible | 0.202% | 496 |
| Admixed American | 0.112% | 896 |
| European (non-Finnish) | 0.103% | 966 |
| South Asian | 0.0944% | 1,059 |
| African / African-American | 0.0213% | 4,691 |
| Finnishnot grpmax-eligible | 0.00938% | 10,656 |
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
- NAAA
- Protein
- p.Ile80=
- Coding
- c.240C>T
- MANE Select
- NM_014435
- dbSNP
- rs192282293
- Type
- single nucleotide variant
- Location
- chr4:75940132 (GRCh38)
- Gene constraint
- LOEUF 1.14 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 92.67 · 2 PDB
- Residue 80
- an α-helix
Similar variants
- NAAA c.667-7C>T Benign ★★ same type
- NAAA p.Thr262= Benign ★★ same type
- NAAA p.Ala119Asp Uncertain significance ★ ⚠ same type
- NAAA p.Ala314Val Uncertain significance ★ ⚠ same type
- NAAA p.Arg100His Uncertain significance ★ ⚠ same type
- NAAA p.Arg196Gln Uncertain significance ★ ⚠ same type
- NAAA p.Arg256Trp Uncertain significance ★ ⚠ same type
- NAAA p.Arg300Gln 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/naaa-p-ile80 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown