TMTC3 p.Pro275=
c.825A>G · rs139775413 · VCV717658
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0252%, nfe)
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 2.1 | GERP -0.35, phastCons 1 |
| Overall | ||
| CADD | 9.613 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0252%
European (non-Finnish) · 297/1,179,910 alleles
Filtering AF
0.0228%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0218%
Overall
0.0195%
314/1,613,930 alleles · ultra-rare
exomes 294/1,461,660 · genomes 20/152,270 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.0252% | 3,973 |
| Remaining individualsnot grpmax-eligible | 0.016% | 6,249 |
| Admixed American | 0.00833% | 11,998 |
| Ashkenazi Jewishnot grpmax-eligible | 0.00338% | 29,590 |
| African / African-American | 0.00133% | 75,038 |
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
- TMTC3
- Protein
- p.Pro275=
- Coding
- c.825A>G
- MANE Select
- NM_181783
- dbSNP
- rs139775413
- Type
- single nucleotide variant
- Location
- chr12:88166357 (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-pro275 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown