TAC3 p.Pro77=
c.231C>T · rs201828127 · VCV2055737
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00966%, 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 2.3 | GERP -2.4, phastCons 1 |
| Overall | ||
| CADD | 8.099 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00966%
European (non-Finnish) · 114/1,179,942 alleles
Filtering AF
0.00817%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00761%
Overall
0.00793%
128/1,613,928 alleles · very rare
exomes 120/1,461,732 · genomes 8/152,196 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00966% | 10,350 |
| Finnishnot grpmax-eligible | 0.00937% | 10,672 |
| Remaining individualsnot grpmax-eligible | 0.0064% | 15,617 |
| African / African-American | 0.00401% | 24,968 |
| Admixed American | 0.00167% | 59,998 |
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
- TAC3
- Protein
- p.Pro77=
- Coding
- c.231C>T
- MANE Select
- NM_013251
- dbSNP
- rs201828127
- Type
- single nucleotide variant
- Location
- chr12:57013366 (GRCh38)
- Gene constraint
- LOEUF 0.927 · pLI 0.04 (gnomAD)
- Structure
- AlphaFold pLDDT 65.34 · 2 PDB
Similar variants
- TAC3 p.Gln45Arg Uncertain significance ★★ ⚠ same type
- TAC3 c.114+87G>T Benign ★★ same type
- TAC3 c.292+162A>G Benign ★★ same type
- TAC3 c.*19C>T Benign ★★ same type
- TAC3 p.Ser99Pro Benign ★★ same type
- TAC3 c.238+1G>C Likely pathogenic ★ same type
- TAC3 p.Arg80Ser Likely pathogenic ★ same type
- TAC3 c.209-1G>C Conflicting classifications of pathogenicity ★ 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/tac3-p-pro77 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown