TMTC3 p.Leu725=
c.2175G>A · rs2502044807 · VCV2078966
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Absent
absent from gnomAD v4.1
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 1.5 | GERP -0.98, phastCons 1 |
| Overall | ||
| CADD | 4.535 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.
Variant & gene context
- Gene
- TMTC3
- Protein
- p.Leu725=
- Coding
- c.2175G>A
- MANE Select
- NM_181783
- dbSNP
- rs2502044807
- Type
- single nucleotide variant
- Location
- chr12:88195079 (GRCh38)
- Gene constraint
- LOEUF 0.721 · pLI <0.01 (gnomAD)
- Structure
- AlphaFold pLDDT 87.83
Similar variants
- TMTC3 p.Arg319Ter Pathogenic/Likely pathogenic ★★ same type
- TMTC3 p.Arg656Ter Pathogenic ★★ same type
- TMTC3 p.Ala540Glu Uncertain significance ★★ same type
- TMTC3 p.Arg553Cys Uncertain significance ★★ same type
- TMTC3 p.Asp427Tyr Uncertain significance ★★ same type
- TMTC3 p.Asp561Asn Uncertain significance ★★ same type
- TMTC3 p.Cys778Tyr Uncertain significance ★★ same type
- TMTC3 p.Glu299Gln 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/tmtc3-p-leu725 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown