TTN p.Pro3954=
c.11862T>A · rs749519968 · VCV1567676
Likely benign
Multiple submitters
Classification
Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 2 submitters
gnomAD v4.1
Rare
very rare (popmax 0.00833%, amr)
Conditions
3
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 0.29 | GERP -5.7, phastCons 0.37 |
| Overall | ||
| CADD | 3.257 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00833%
Admixed American · 5/60,006 alleles
Filtering AF
0.00323%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.00207%
Overall
0.00031%
5/1,613,910 alleles · very rare
exomes 5/1,461,614 · genomes 0/152,296 · 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.Pro3954=
- Coding
- c.11862T>A
- MANE Select
- NM_001267550
- dbSNP
- rs749519968
- Type
- single nucleotide variant
- Location
- chr2:178741371 (GRCh38)
- Gene constraint
- LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Similar variants
- 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
- TTN c.107377+1G>C 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-pro3954 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown