ENTPD3 p.Ala496=
c.1488G>A · VCV4249298
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0134%, eas)
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 -3.5 | GERP -4.8 |
| Overall | ||
| CADD | 7.324 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0134%
East Asian · 6/44,872 alleles
Filtering AF
0.00579%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00394%
Overall
0.0026%
42/1,613,760 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0134% | 7,479 |
| Remaining individualsnot grpmax-eligible | 0.0096% | 10,415 |
| Admixed American | 0.00667% | 14,998 |
| African / African-American | 0.00401% | 24,907 |
| South Asian | 0.0022% | 45,535 |
| European (non-Finnish) | 0.00178% | 56,191 |
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
- ENTPD3
- Protein
- p.Ala496=
- Coding
- c.1488G>A
- MANE Select
- NM_001248
- Type
- single nucleotide variant
- Location
- chr3:40427406 (GRCh38)
- Gene constraint
- LOEUF 1.454 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 90.79
- Residue 496
- a UniProt-annotated variant site (in)
Similar variants
- ENTPD3 p.Ala140Val Uncertain significance ★ ⚠ same type
- ENTPD3 p.Ala17Ser Uncertain significance ★ ⚠ same type
- ENTPD3 p.Ala223Val Uncertain significance ★ ⚠ same type
- ENTPD3 p.Arg143His Uncertain significance ★ ⚠ same type
- ENTPD3 p.Arg292Gln Uncertain significance ★ ⚠ same type
- ENTPD3 p.Arg292Trp Uncertain significance ★ ⚠ same type
- ENTPD3 p.Arg419Cys Uncertain significance ★ ⚠ same type
- ENTPD3 p.Arg419His 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/entpd3-p-ala496 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown