HEXD p.Pro471=
c.1413C>T · rs745586320 · VCV2617682
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.033%, mid)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.039 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP -1.5 | GERP -2.5 |
| Overall | ||
| CADD | 0.49 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.033%
Middle Eastern · 2/6,066 alleles
Filtering AF
0.00581%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00242%
Overall
0.00186%
30/1,610,756 alleles · ultra-rare
exomes 26/1,458,536 · genomes 4/152,220 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.033% | 3,033 |
| Remaining individualsnot grpmax-eligible | 0.00481% | 20,809 |
| African / African-American | 0.004% | 24,975 |
| Finnishnot grpmax-eligible | 0.00326% | 30,688 |
| East Asian | 0.00223% | 44,888 |
| Admixed American | 0.00167% | 59,976 |
| European (non-Finnish) | 0.00153% | 65,530 |
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
- HEXD
- Protein
- p.Pro471=
- Coding
- c.1413C>T
- MANE Select
- NM_001330542
- dbSNP
- rs745586320
- Type
- single nucleotide variant
- Location
- chr17:82442336 (GRCh38)
- Gene constraint
- LOEUF 1.219 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.50
Similar variants
- HEXD c.632-13G>T Benign ★★ same type
- HEXD p.Ile145Val Benign ★★ same type
- HEXD p.Thr5= Benign ★★ same type
- HEXD c.1061+14A>G Uncertain significance ★ same type
- HEXD c.1061+36C>T Uncertain significance ★ same type
- HEXD c.1061+6C>T Uncertain significance ★ same type
- HEXD c.1062-16G>C Uncertain significance ★ same type
- HEXD c.1062-40C>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/hexd-p-pro471 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown