HIRA p.Ala489=
c.1467G>A · rs116388467 · VCV777553
Benign
Single submitter
Classification
Benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 2.98%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal. | ||
| Splicing | ||
| SpliceAI | Δ0.45 | acceptor gain · deltas |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -4.3 | GERP -3.5 |
| Overall | ||
| CADD | 17.07 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
2.98%
Admixed American · 1,745/58,592 alleles
Filtering AF
2.86%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 2.81%
Overall
0.134%
2,156/1,606,524 alleles · low-frequency
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 2.98% | 34 |
| East Asian | 0.415% | 241 |
| Remaining individualsnot grpmax-eligible | 0.0948% | 1,055 |
| African / African-American | 0.0883% | 1,132 |
| Middle Eastern | 0.0498% | 2,007 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0136% | 7,330 |
| South Asian | 0.01% | 9,979 |
| European (non-Finnish) | 0.00723% | 13,840 |
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
- HIRA
- Protein
- p.Ala489=
- Coding
- c.1467G>A
- MANE Select
- NM_003325
- dbSNP
- rs116388467
- Type
- single nucleotide variant
- Location
- chr22:19378015 (GRCh38)
- Gene constraint
- LOEUF 0.176 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
- Structure
- AlphaFold pLDDT 75.20 · 2 PDB
- Residue 489
- the 'interaction with ccna1' region
Similar variants
- HIRA p.Ala489Val Uncertain significance ★ ⚠ same residue
- HIRA p.Cys723Tyr Uncertain significance ★★ ⚠ same type
- HIRA c.100+84A>G Benign ★★ same type
- HIRA c.1415+91G>A Benign ★★ same type
- HIRA c.1613+106A>G Benign ★★ same type
- HIRA c.1614-3C>T Likely benign ★★ same type
- HIRA c.1776-136C>G Benign ★★ same type
- HIRA c.1981-42T>C Benign ★★ 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/hira-p-ala489 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown