TTN p.Pro5357=
c.16071A>G · rs1251542501 · VCV626451
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
ultra-rare (popmax 0.0168%, mid)
Conditions
1
cardiomyopathy
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 -8.7 | GERP -5.8 |
| Overall | ||
| CADD | 0.533 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.0168%
Middle Eastern · 1/5,970 alleles
Overall
0.000139%
2/1,443,060 alleles · ultra-rare
| Ancestry group | Frequency | 1 in |
|---|---|---|
| Middle Easterngrpmax | 0.0168% | 5,970 |
| European (non-Finnish) | 8.56e-05% | 1,168,866 |
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.Pro5357=
- Coding
- c.16071A>G
- MANE Select
- NM_001267550
- dbSNP
- rs1251542501
- Type
- single nucleotide variant
- Location
- chr2:178733105 (GRCh38)
- Gene constraint
- LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Residue 5357
- the ig-like 34 domain
Similar variants
- TTN c.2775+1G>T Likely pathogenic ★★ same condition
- TTN c.54811+1G>A Likely pathogenic ★★ same condition
- TTN c.58732+2T>C Likely pathogenic ★★ same condition
- TTN c.67349-2A>C Pathogenic/Likely pathogenic ★★ same condition
- TTN c.86821+2T>A Pathogenic/Likely pathogenic ★★ same condition
- TTN c.97492+1G>C Pathogenic/Likely pathogenic ★★ same condition
- TTN p.Arg14069Ter Pathogenic/Likely pathogenic ★★ same condition
- TTN p.Arg14079Ter 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-pro5357 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown