Is TTN p.Pro13033= (c.39099T>C) pathogenic?

TTN p.Pro13033= (c.39099T>C) is classified Conflicting classifications of pathogenicity in TTN (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-04-01). Rare (popmax 0.132%, mid); Associated with autosomal recessive limb-girdle muscular dystrophy type 2J.

How common is TTN p.Pro13033= (c.39099T>C) in the general population?

TTN p.Pro13033= (c.39099T>C) is rare (popmax 0.132%, mid) (gnomAD).

How is Titin-related limb-girdle muscular dystrophy R10 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

TTN p.Pro13033=

Q: What condition is associated with TTN p.Pro13033= (c.39099T>C)?

TTN p.Pro13033= (c.39099T>C) is associated with autosomal recessive limb-girdle muscular dystrophy type 2J, dilated cardiomyopathy 1G (ClinVar).

c.39099T>C · rs755793186 · VCV467106

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.132%, mid)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2J

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 0.098	GERP -3.7, phastCons 0.14
Overall
CADD	1.871	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.132% Middle Eastern · 8/6,074 alleles

Filtering AF 0.0655% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0478%

Overall 0.00694% 112/1,613,498 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.132%	759
South Asian	0.0615%	1,626
Ashkenazi Jewishnot grpmax-eligible	0.0608%	1,644
Remaining individualsnot grpmax-eligible	0.0208%	4,803
European (non-Finnish)	0.00144%	69,391

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.Pro13033=
Coding: c.39099T>C
MANE Select: NM_001267550
dbSNP: rs755793186
Type: single nucleotide variant
Location: chr2:178652486 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)

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

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2J — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 1G

For Titin-related limb-girdle muscular dystrophy R10 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

Similar variants

TTN p.Pro13033Leu Uncertain significance ★ ⚠ same residue
TTN p.Pro13033Ala Uncertain significance ★ ⚠ same residue
TTN p.Pro13033Thr 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

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-pro13033 (accessed [today's date]).

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