EXPH5 p.Glu596=
c.1788G>A · rs141242849 · VCV2749735
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0292%, nfe)
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| Splicing | ||
| SpliceAI | <0.2 | no splice effect predicted · four deltas, not one · how we know |
|---|---|---|
| Constraint at this position | ||
| Conservation | phyloP -0.89 | GERP -2.9 |
| Overall | ||
| CADD | 0.307 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0292%
European (non-Finnish) · 344/1,179,478 alleles
Filtering AF
0.0265%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0256%
Overall
0.0229%
370/1,612,412 alleles · ultra-rare
exomes 353/1,460,200 · genomes 17/152,212 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0292% | 3,429 |
| Remaining individualsnot grpmax-eligible | 0.0256% | 3,901 |
| Admixed American | 0.01% | 9,960 |
| Ashkenazi Jewishnot grpmax-eligible | 0.0034% | 29,448 |
| Finnishnot grpmax-eligible | 0.00313% | 31,977 |
| African / African-American | 0.00134% | 74,832 |
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.Glu596=
- Coding
- c.1788G>A
- MANE Select
- NM_015065
- dbSNP
- rs141242849
- Type
- single nucleotide variant
- Location
- chr11:108513719 (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-glu596 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown