Is TTN p.Asp5352= (c.16056T>C) pathogenic?

TTN p.Asp5352= (c.16056T>C) is classified Conflicting classifications of pathogenicity in TTN (ClinVar, Conflicting submitters, 12 submitters; last evaluated 2026-01-27). Ultra-rare (popmax 0.0584%, eas); Associated with cardiomyopathy.

What condition is associated with TTN p.Asp5352= (c.16056T>C)?

TTN p.Asp5352= (c.16056T>C) is associated with cardiomyopathy, tibial muscular dystrophy, myopathy, myofibrillar, 9, with early respiratory failure (ClinVar).

How common is TTN p.Asp5352= (c.16056T>C) in the general population?

TTN p.Asp5352= (c.16056T>C) is ultra-rare (popmax 0.0584%, eas) (gnomAD).

TTN p.Asp5352=

c.16056T>C · rs376820575 · VCV332930

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 12 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0584%, eas)

Conditions

cardiomyopathy

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 7.1	GERP 2.9, phastCons 1
Overall
CADD	12.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0584% East Asian · 26/44,492 alleles

Filtering AF 0.0409% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.035%

Overall 0.00473% 75/1,585,690 alleles · ultra-rare exomes 64/1,433,396 · genomes 11/152,294 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0584%	1,711
South Asian	0.0338%	2,958
Remaining individualsnot grpmax-eligible	0.0212%	4,710
Middle Eastern	0.0169%	5,918
Admixed American	0.00344%	29,069
European (non-Finnish)	0.000344%	291,084

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.Asp5352=
Coding: c.16056T>C
MANE Select: NM_001267550
dbSNP: rs376820575
Type: single nucleotide variant
Location: chr2:178733120 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 5352: the ig-like 34 domain

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

Also linked: 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.Asp5352Asn Pathogenic/Likely pathogenic ★★ ⚠ 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
TTN c.107377+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-asp5352 (accessed [today's date]).

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