Is TTN p.Pro11= (c.33G>A) pathogenic?

TTN p.Pro11= (c.33G>A) is classified Conflicting classifications of pathogenicity in TTN (ClinVar, Conflicting submitters, 16 submitters; last evaluated 2026-01-18). Rare (popmax 0.109%, eas); Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Pro11= (c.33G>A)?

TTN p.Pro11= (c.33G>A) is associated with Cardiovascular phenotype, cardiomyopathy, tibial muscular dystrophy (ClinVar).

How common is TTN p.Pro11= (c.33G>A) in the general population?

TTN p.Pro11= (c.33G>A) is rare (popmax 0.109%, eas) (gnomAD).

TTN p.Pro11=

c.33G>A · rs138331646 · VCV46948

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 16 submitters

gnomAD v4.1

Rare

rare (popmax 0.109%, eas)

Conditions

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 1.4	GERP 2.3, phastCons 1
Overall
CADD	17.77	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.109% East Asian · 49/44,872 alleles

Filtering AF 0.0848% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0785%

Overall 0.067% 1,081/1,613,834 alleles · rare exomes 1,017/1,461,682 · genomes 64/152,152 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.109%	916
European (non-Finnish)	0.0847%	1,181
Remaining individualsnot grpmax-eligible	0.032%	3,123
Middle Eastern	0.0165%	6,072
African / African-American	0.00801%	12,484
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,600
Admixed American	0.00333%	29,996
Finnishnot grpmax-eligible	0.00312%	32,015
South Asian	0.0011%	91,048

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.Pro11=
Coding: c.33G>A
MANE Select: NM_001267550
dbSNP: rs138331646
Type: single nucleotide variant
Location: chr2:178804610 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 11: the ig-like 1 domain

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

Disease context

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

Also linked: cardiomyopathy tibial muscular dystrophy myopathy, myofibrillar, 9, with early respiratory failure dilated cardiomyopathy 1G autosomal recessive limb-girdle muscular dystrophy type 2J early-onset myopathy with fatal cardiomyopathy

Similar variants

TTN p.Pro11Leu Uncertain significance ★★ same residue
TTN p.Pro11Ser Uncertain significance ★ 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

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-pro11 (accessed [today's date]).

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