Is TTN p.Ala142= (c.426C>T) pathogenic?

TTN p.Ala142= (c.426C>T) is classified Benign/Likely benign in TTN (ClinVar, Multiple submitters, 19 submitters; last evaluated 2026-02-03). Low-frequency (popmax 2.24%, sas); Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Ala142= (c.426C>T)?

TTN p.Ala142= (c.426C>T) is associated with Cardiovascular phenotype, cardiomyopathy, tibial muscular dystrophy (ClinVar).

How common is TTN p.Ala142= (c.426C>T) in the general population?

TTN p.Ala142= (c.426C>T) is low-frequency (popmax 2.24%, sas) (gnomAD).

TTN p.Ala142=

c.426C>T · rs56137037 · VCV47044

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 19 submitters

gnomAD v4.1

Rare

low-frequency (popmax 2.24%, sas)

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 -3.3	GERP -4.3
Overall
CADD	3.668	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 2.24% South Asian · 2,037/91,078 alleles

Filtering AF 2.16% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.12%

Overall 0.244% 3,938/1,614,108 alleles · low-frequency exomes 3,631/1,461,846 · genomes 307/152,262 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	2.24%	45
Ashkenazi Jewishnot grpmax-eligible	0.77%	130
Middle Eastern	0.413%	242
Remaining individualsnot grpmax-eligible	0.314%	319
European (non-Finnish)	0.115%	867
Admixed American	0.103%	968
African / African-American	0.028%	3,573
East Asian	0.00891%	11,220
Finnishnot grpmax-eligible	0.00625%	16,008

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.Ala142=
Coding: c.426C>T
MANE Select: NM_001267550
dbSNP: rs56137037
Type: single nucleotide variant
Location: chr2:178800552 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 142: the ig-like 2 domain; a β-strand

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-ala142 (accessed [today's date]).

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