Is TTN p.Pro22141= (c.66423C>T) pathogenic?

TTN p.Pro22141= (c.66423C>T) is classified Conflicting classifications of pathogenicity in TTN (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2023-10-10). Very rare (popmax 0.00267%, afr); Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Pro22141= (c.66423C>T)?

TTN p.Pro22141= (c.66423C>T) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How common is TTN p.Pro22141= (c.66423C>T) in the general population?

TTN p.Pro22141= (c.66423C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

TTN p.Pro22141=

c.66423C>T · rs1322620894 · VCV597332

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.5	GERP -1.2, phastCons 1
Overall
CADD	1.943	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,882 alleles

Filtering AF 0.000443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000124% 2/1,613,126 alleles · very rare exomes 1/1,461,024 · genomes 1/152,102 · joint denominator

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.Pro22141=
Coding: c.66423C>T
MANE Select: NM_001267550
dbSNP: rs1322620894
Type: single nucleotide variant
Location: chr2:178581946 (GRCh38)

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: dilated cardiomyopathy 1G autosomal recessive limb-girdle muscular dystrophy type 2J

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-pro22141 (accessed [today's date]).

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