TTN p.Pro28079=
c.84237A>C · VCV4866182
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 8.48e-05%, nfe)
Conditions
1
Cardiovascular phenotype
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 2.4 | GERP 2.9, phastCons 1 |
| Overall | ||
| CADD | 0.743 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
8.48e-05%
European (non-Finnish) · 1/1,179,720 alleles
Overall
6.2e-05%
1/1,613,496 alleles · very rare
exomes 0/1,461,316 · genomes 1/152,180 · 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
- TTN
- Protein
- p.Pro28079=
- Coding
- c.84237A>C
- MANE Select
- NM_001267550
- Type
- single nucleotide variant
- Location
- chr2:178561895 (GRCh38)
- Gene constraint
- LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Residue 28079
- the fibronectin type-iii 104 domain
Similar variants
- TTN c.107377+1G>C Pathogenic/Likely pathogenic ★★ same condition
- TTN c.54190+1G>A Pathogenic/Likely pathogenic ★★ same condition
- TTN c.54811+1G>A Likely pathogenic ★★ same condition
- TTN c.57112-1G>A Likely pathogenic ★★ same condition
- TTN c.58732+2T>C Likely pathogenic ★★ same condition
- TTN c.95723-2A>C Likely pathogenic ★★ same condition
- TTN p.Arg1012Ter Pathogenic/Likely pathogenic ★★ same condition
- TTN p.Arg14069Ter Pathogenic/Likely pathogenic ★★ same condition
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/ttn-p-pro28079 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown