Is TTN p.Pro17138= (c.51414A>G) pathogenic?

TTN p.Pro17138= (c.51414A>G) is classified Likely benign in TTN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-14). Very rare (popmax 0.00611%, nfe); Associated with dilated cardiomyopathy 1G.

What condition is associated with TTN p.Pro17138= (c.51414A>G)?

TTN p.Pro17138= (c.51414A>G) is associated with dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How common is TTN p.Pro17138= (c.51414A>G) in the general population?

TTN p.Pro17138= (c.51414A>G) is very rare (popmax 0.00611%, nfe) (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.Pro17138=

c.51414A>G · rs376459830 · VCV1097954

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00611%, nfe)

Conditions

dilated cardiomyopathy 1G

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 0.16	GERP -5.2, phastCons 0.009
Overall
CADD	1.731	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00611% European (non-Finnish) · 72/1,179,318 alleles

Filtering AF 0.00495% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00455%

Overall 0.00453% 73/1,612,754 alleles · very rare exomes 71/1,460,754 · genomes 2/152,000 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00611%	16,379
Remaining individualsnot grpmax-eligible	0.0016%	62,396

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.Pro17138=
Coding: c.51414A>G
MANE Select: NM_001267550
dbSNP: rs376459830
Type: single nucleotide variant
Location: chr2:178610112 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 17138: the ig-like 102 domain

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-pro17138 (accessed [today's date]).

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