Is TTN p.Pro11051Ser (c.33151C>T) pathogenic?

TTN p.Pro11051Ser (c.33151C>T) is classified Uncertain significance in TTN (ClinVar, Single submitter, 1 submitter; last evaluated 2016-09-23). AlphaMissense: likely benign (0.2188); Absent from gnomAD v4.1; Associated with cardiomyopathy.

What condition is associated with TTN p.Pro11051Ser (c.33151C>T)?

TTN p.Pro11051Ser (c.33151C>T) is associated with cardiomyopathy (ClinVar).

How common is TTN p.Pro11051Ser (c.33151C>T) in the general population?

TTN p.Pro11051Ser (c.33151C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about TTN p.Pro11051Ser (c.33151C>T)?

AlphaMissense predicts likely benign (score 0.2188) — an in-silico prediction, not a clinical call.

TTN p.Pro11051Ser

c.33151C>T · rs1560337533 · VCV626688

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2188 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

cardiomyopathy

Computational evidence

Protein change
AlphaMissense	0.2188	likely benign
REVEL	0.269	benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.9	GERP 2.6, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 141 kb · p 0.23 · regional, not allelic
Overall
CADD	21.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P10734S vs ClinVar P11051S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TTN
Protein: p.Pro11051Ser
Coding: c.33151C>T
MANE Select: NM_001267550
dbSNP: rs1560337533
Type: single nucleotide variant
Location: chr2:178681682 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 11051: the 'disordered' region

Full TTN gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

cardiomyopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

TTN p.Pro11051Arg Uncertain significance ★ same residue
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

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-pro11051ser (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown