Is TTN p.Pro28151= (c.84453A>G) pathogenic?

TTN p.Pro28151= (c.84453A>G) is classified Benign/Likely benign in TTN (ClinVar, Multiple submitters, 19 submitters; last evaluated 2026-02-03). Low-frequency (popmax 3.27%, afr); Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Pro28151= (c.84453A>G)?

TTN p.Pro28151= (c.84453A>G) is associated with Cardiovascular phenotype, cardiomyopathy, tibial muscular dystrophy (ClinVar).

How common is TTN p.Pro28151= (c.84453A>G) in the general population?

TTN p.Pro28151= (c.84453A>G) is low-frequency (popmax 3.27%, afr) (gnomAD).

TTN p.Pro28151=

c.84453A>G · rs73036373 · VCV47436

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 19 submitters

gnomAD v4.1

Rare

low-frequency (popmax 3.27%, afr)

Conditions

Cardiovascular phenotype

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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 -0.77	GERP -2.1, phastCons 0.018
Overall
CADD	0.263	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 3.27% African / African-American · 2,449/74,820 alleles

Filtering AF 3.17% ClinGen BA1/BS1 input FAF95, joint · FAF99 3.12%

Overall 0.212% 3,407/1,607,268 alleles · low-frequency exomes 1,961/1,454,958 · genomes 1,446/152,310 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	3.27%	31
Ashkenazi Jewishnot grpmax-eligible	0.69%	145
Admixed American	0.282%	355
Remaining individualsnot grpmax-eligible	0.281%	355
Middle Eastern	0.249%	401
European (non-Finnish)	0.0336%	2,977
South Asian	0.00332%	30,099

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.Pro28151=
Coding: c.84453A>G
MANE Select: NM_001267550
dbSNP: rs73036373
Type: single nucleotide variant
Location: chr2:178561679 (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: 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

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-pro28151 (accessed [today's date]).

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