Is TTN p.Pro29537= (c.88611T>G) pathogenic?

TTN p.Pro29537= (c.88611T>G) is classified Conflicting classifications of pathogenicity in TTN (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-02-03). Rare (popmax 0.401%, eas); Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Pro29537= (c.88611T>G)?

TTN p.Pro29537= (c.88611T>G) is associated with Cardiovascular phenotype, cardiomyopathy, tibial muscular dystrophy (ClinVar).

How common is TTN p.Pro29537= (c.88611T>G) in the general population?

TTN p.Pro29537= (c.88611T>G) is rare (popmax 0.401%, eas) (gnomAD).

TTN p.Pro29537=

c.88611T>G · rs555380931 · VCV413106

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.401%, 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 -0.94	GERP -5.9, phastCons 0.006
Overall
CADD	6.528	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.401% East Asian · 180/44,872 alleles

Filtering AF 0.353% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.335%

Overall 0.0134% 217/1,613,794 alleles · rare exomes 186/1,461,470 · genomes 31/152,324 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.401%	249
South Asian	0.0253%	3,957
Remaining individualsnot grpmax-eligible	0.0176%	5,679
Admixed American	0.00167%	60,006
European (non-Finnish)	0.00017%	589,901

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.Pro29537=
Coding: c.88611T>G
MANE Select: NM_001267550
dbSNP: rs555380931
Type: single nucleotide variant
Location: chr2:178554736 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 29537: the fibronectin type-iii 115 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 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-pro29537 (accessed [today's date]).

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