EXPH5 p.Arg459=
c.1377A>G · rs116565594 · VCV785382
Benign
Multiple submitters
Classification
Benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 3 submitters
gnomAD v4.1
Rare
low-frequency (popmax 3.75%, afr)
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 -0.084 | GERP -3.9, phastCons 0.005 |
| Overall | ||
| CADD | 3.858 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
3.75%
African / African-American · 2,813/74,996 alleles
Filtering AF
3.64%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 3.59%
Overall
0.199%
3,208/1,613,708 alleles · low-frequency
exomes 1,568/1,461,422 · genomes 1,640/152,286 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 3.75% | 27 |
| Remaining individualsnot grpmax-eligible | 0.294% | 340 |
| Admixed American | 0.27% | 370 |
| Middle Eastern | 0.165% | 606 |
| South Asian | 0.0154% | 6,498 |
| European (non-Finnish) | 0.00212% | 47,195 |
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
- EXPH5
- Protein
- p.Arg459=
- Coding
- c.1377A>G
- MANE Select
- NM_015065
- dbSNP
- rs116565594
- Type
- single nucleotide variant
- Location
- chr11:108514130 (GRCh38)
- Gene constraint
- LOEUF 1.142 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 36.39
Similar variants
- EXPH5 p.Ala1429Ser Uncertain significance ★★ ⚠ same type
- EXPH5 p.Arg1727Lys Uncertain significance ★★ ⚠ same type
- EXPH5 p.Asn1548Asp Uncertain significance ★★ ⚠ same type
- EXPH5 p.Asp741His Uncertain significance ★★ ⚠ same type
- EXPH5 p.Gln1464Arg Uncertain significance ★★ ⚠ same type
- EXPH5 p.Gly54Arg Uncertain significance ★★ ⚠ same type
- EXPH5 p.Leu1519Arg Uncertain significance ★★ ⚠ same type
- EXPH5 p.Leu234Phe 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/exph5-p-arg459 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown