Is TTN p.Pro8264= (c.24792G>A) pathogenic?

TTN p.Pro8264= (c.24792G>A) is classified Conflicting classifications of pathogenicity in TTN (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-31). Ultra-rare (popmax 0.0215%, afr); Associated with autosomal recessive limb-girdle muscular dystrophy type 2J.

How common is TTN p.Pro8264= (c.24792G>A) in the general population?

TTN p.Pro8264= (c.24792G>A) is ultra-rare (popmax 0.0215%, 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.Pro8264=

Q: What condition is associated with TTN p.Pro8264= (c.24792G>A)?

TTN p.Pro8264= (c.24792G>A) is associated with autosomal recessive limb-girdle muscular dystrophy type 2J, dilated cardiomyopathy 1G (ClinVar).

c.24792G>A · rs767137418 · VCV282099

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0215%, afr)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2J

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.17	GERP -5.6, phastCons 0.18
Overall
CADD	1.789	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0215% African / African-American · 16/74,570 alleles

Filtering AF 0.0134% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.00638% 102/1,598,478 alleles · ultra-rare exomes 96/1,446,448 · genomes 6/152,030 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0215%	4,661
East Asian	0.0067%	14,925
European (non-Finnish)	0.00655%	15,266
Remaining individualsnot grpmax-eligible	0.00483%	20,691
South Asian	0.00222%	44,982
Admixed American	0.00168%	59,472

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.Pro8264=
Coding: c.24792G>A
MANE Select: NM_001267550
dbSNP: rs767137418
Type: single nucleotide variant
Location: chr2:178718214 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 8264: the ig-like 65 domain; a β-strand

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

Similar variants

TTN p.Pro8264Ser Uncertain significance ★ same residue
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

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-pro8264 (accessed [today's date]).

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