Is TTN p.Pro21452= (c.64356A>G) pathogenic?

TTN p.Pro21452= (c.64356A>G) is classified Likely benign in TTN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-05-09). Very rare (popmax 0.00267%, afr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2J.

How common is TTN p.Pro21452= (c.64356A>G) in the general population?

TTN p.Pro21452= (c.64356A>G) is very rare (popmax 0.00267%, afr) (gnomAD).

How is Titin-related limb-girdle muscular dystrophy R10 inherited?

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

TTN p.Pro21452=

Q: What condition is associated with TTN p.Pro21452= (c.64356A>G)?

TTN p.Pro21452= (c.64356A>G) is associated with autosomal recessive limb-girdle muscular dystrophy type 2J, dilated cardiomyopathy 1G (ClinVar).

c.64356A>G · rs1431828617 · VCV1557967

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2J

⚠ 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 -1.3	GERP -5.7, phastCons 0.001
Overall
CADD	0.482	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00267% African / African-American · 2/74,892 alleles

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

Overall 0.00031% 5/1,613,112 alleles · very rare exomes 2/1,461,008 · genomes 3/152,104 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,446
European (non-Finnish)	0.000254%	393,128

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.Pro21452=
Coding: c.64356A>G
MANE Select: NM_001267550
dbSNP: rs1431828617
Type: single nucleotide variant
Location: chr2:178586545 (GRCh38)

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

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2J — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 1G

For Titin-related limb-girdle muscular dystrophy R10 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Adult, Childhood

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-pro21452 (accessed [today's date]).

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