Is TTN p.Ala4792= (c.14376A>T) pathogenic?

TTN p.Ala4792= (c.14376A>T) is classified Likely benign in TTN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-26). Absent from gnomAD v4.1; Associated with dilated cardiomyopathy 1G.

What condition is associated with TTN p.Ala4792= (c.14376A>T)?

TTN p.Ala4792= (c.14376A>T) is associated with dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How common is TTN p.Ala4792= (c.14376A>T) in the general population?

TTN p.Ala4792= (c.14376A>T) is absent from gnomAD v4.1 (gnomAD).

How is Familial isolated dilated cardiomyopathy inherited?

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

TTN p.Ala4792=

c.14376A>T · rs2154314578 · VCV1568746

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

dilated cardiomyopathy 1G

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.20	acceptor gain · deltas
Constraint at this position
Conservation	phyloP -5.5	GERP -5.4
Overall
CADD	2.918	PHRED · no single calibrated threshold — expert panels disagree

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.Ala4792=
Coding: c.14376A>T
MANE Select: NM_001267550
dbSNP: rs2154314578
Type: single nucleotide variant
Location: chr2:178736070 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 4792: the ig-like 28 domain; a disulfide bond

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

Disease context

dilated cardiomyopathy 1G — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive limb-girdle muscular dystrophy type 2J

For Familial isolated dilated cardiomyopathy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, Mitochondrial inheritance
Onset: All ages
Prevalence: 1-9 / 100 000 (Europe)

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-ala4792 (accessed [today's date]).

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