TTN p.Pro28451=
c.85353T>G · rs1703355762 · VCV3223315
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.0022%, sas)
Conditions
1
Cardiovascular phenotype
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 2.7 | GERP -0.59, phastCons 1 |
| Overall | ||
| CADD | 0.537 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0022%
South Asian · 2/91,080 alleles
Filtering AF
0.000365%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.000137%
Overall
0.000186%
3/1,613,760 alleles · very rare
exomes 3/1,461,448 · genomes 0/152,312 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| South Asiangrpmax | 0.0022% | 45,540 |
| European (non-Finnish) | 8.48e-05% | 1,179,798 |
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.Pro28451=
- Coding
- c.85353T>G
- MANE Select
- NM_001267550
- dbSNP
- rs1703355762
- Type
- single nucleotide variant
- Location
- chr2:178560779 (GRCh38)
- Gene constraint
- LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Residue 28451
- the fibronectin type-iii 107 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-pro28451 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown