HEXD p.Pro472=
c.1416G>A · rs774339234 · VCV3105549
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0217%, amr)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.013 | strongly benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
| Constraint at this position | ||
| Conservation | phyloP -0.56 | GERP -2.2 |
| Overall | ||
| CADD | 1.557 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0217%
Admixed American · 13/59,974 alleles
Filtering AF
0.0128%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0101%
Overall
0.00267%
43/1,610,602 alleles · ultra-rare
exomes 41/1,458,424 · genomes 2/152,178 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Admixed Americangrpmax | 0.0217% | 4,613 |
| African / African-American | 0.00534% | 18,728 |
| Remaining individualsnot grpmax-eligible | 0.0032% | 31,204 |
| European (non-Finnish) | 0.00187% | 53,612 |
| Finnishnot grpmax-eligible | 0.00163% | 61,360 |
| South Asian | 0.0011% | 91,070 |
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.Pro472=
- Coding
- c.1416G>A
- MANE Select
- NM_001330542
- dbSNP
- rs774339234
- Type
- single nucleotide variant
- Location
- chr17:82442339 (GRCh38)
- Gene constraint
- LOEUF 1.219 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 93.50
Similar variants
- HEXD p.Pro472Leu Uncertain significance ★ ⚠ same residue
- 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
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-pro472 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown