TAPT1 p.Leu499=
c.1497G>A · rs368111048 · VCV3006665
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000254%, 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 0.6 | GERP 0.18, phastCons 1 |
| Overall | ||
| CADD | 6.019 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000254%
European (non-Finnish) · 3/1,179,708 alleles
Filtering AF
6.8e-05%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 1.9e-05%
Overall
0.000186%
3/1,613,622 alleles · very rare
exomes 0/1,461,460 · genomes 3/152,162 · joint denominator
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
- TAPT1
- Protein
- p.Leu499=
- Coding
- c.1497G>A
- MANE Select
- NM_153365
- dbSNP
- rs368111048
- Type
- single nucleotide variant
- Location
- chr4:16163515 (GRCh38)
- Gene constraint
- LOEUF 0.698 · pLI 0.13 (gnomAD)
- Structure
- AlphaFold pLDDT 71.98
- Residue 499
- the 'disordered' region
Similar variants
- TAPT1 p.Ala122Val Uncertain significance ★★ ⚠ same type
- TAPT1 p.Ala472Thr Uncertain significance ★★ ⚠ same type
- TAPT1 p.Gly15Cys Uncertain significance ★★ ⚠ same type
- TAPT1 p.Gly492Ser Uncertain significance ★★ ⚠ same type
- TAPT1 p.Lys90Arg Uncertain significance ★★ ⚠ same type
- TAPT1 p.Met202Val Uncertain significance ★★ ⚠ same type
- TAPT1 p.Met344Ile Uncertain significance ★★ ⚠ same type
- TAPT1 p.Ser490Ala 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/tapt1-p-leu499 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown