TMTC3 p.Ser231=
c.693T>C · rs183127275 · VCV2983461
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0826%, 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 0.86 | GERP 1, phastCons 1 |
| Overall | ||
| CADD | 9.526 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0826%
East Asian · 37/44,784 alleles
Filtering AF
0.0616%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0543%
Overall
0.00254%
41/1,613,706 alleles · ultra-rare
exomes 35/1,461,434 · genomes 6/152,272 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| East Asiangrpmax | 0.0826% | 1,210 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,621 |
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.Ser231=
- Coding
- c.693T>C
- MANE Select
- NM_181783
- dbSNP
- rs183127275
- Type
- single nucleotide variant
- Location
- chr12:88160747 (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-ser231 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown