TTN p.Pro12973Arg
c.38918C>G · rs907757552 · VCV2584621
Uncertain significance
Single submitter
Classification
Uncertain significance
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.000424%, nfe)
Conditions
2
hypertrophic cardiomyopathy 9
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 -1.7 | GERP 1 |
| Regional constraint | o/e 1.14 | unconstrained · MANE · 14 kb · p 5e-05 · regional, not allelic |
| Overall | ||
| CADD | 11.56 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.000424%
European (non-Finnish) · 5/1,178,980 alleles
Filtering AF
0.000124%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 9e-05%
Overall
0.000343%
5/1,459,184 alleles · very rare
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.Pro12973Arg
- Coding
- c.38918C>G
- MANE Select
- NM_001267550
- dbSNP
- rs907757552
- Type
- single nucleotide variant
- Location
- chr2:178652889 (GRCh38)
- Gene constraint
- LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
- Residue 12973
- the ig-like 86 domain; a disulfide bond
Similar variants
- TTN p.Pro12973= Likely benign ★ same residue
- TTN c.100171+1G>A Likely pathogenic ★★ same condition
- TTN c.100766-1G>T Likely pathogenic ★★ same condition
- TTN c.100766-2A>T Likely pathogenic ★★ same condition
- TTN c.106375-2A>G Pathogenic/Likely pathogenic ★★ same condition
- TTN c.106531+1G>A Pathogenic/Likely pathogenic ★★ same condition
- TTN c.107224-1G>C Pathogenic/Likely pathogenic ★★ same condition
- TTN c.107377+1G>A 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-pro12973arg (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown