Is TTN p.Pro972= (c.2916G>A) pathogenic?

TTN p.Pro972= (c.2916G>A) is classified Conflicting classifications of pathogenicity in TTN (ClinVar, Conflicting submitters, 7 submitters; last evaluated 2026-01-19). Ultra-rare (popmax 0.0703%, sas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2J.

How common is TTN p.Pro972= (c.2916G>A) in the general population?

TTN p.Pro972= (c.2916G>A) is ultra-rare (popmax 0.0703%, sas) (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.Pro972=

Q: What condition is associated with TTN p.Pro972= (c.2916G>A)?

TTN p.Pro972= (c.2916G>A) is associated with autosomal recessive limb-girdle muscular dystrophy type 2J, dilated cardiomyopathy 1G (ClinVar).

c.2916G>A · rs757569345 · VCV466984

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0703%, sas)

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	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.8	GERP -4.6
Overall
CADD	4.176	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0703% South Asian · 64/91,076 alleles

Filtering AF 0.0565% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0514%

Overall 0.00781% 126/1,614,106 alleles · ultra-rare exomes 121/1,461,820 · genomes 5/152,286 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0703%	1,423
Middle Eastern	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0096%	10,418
European (non-Finnish)	0.00424%	23,600
Admixed American	0.00333%	30,008
East Asian	0.00223%	44,878
Finnishnot grpmax-eligible	0.00156%	64,018
African / African-American	0.00133%	75,036

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.Pro972=
Coding: c.2916G>A
MANE Select: NM_001267550
dbSNP: rs757569345
Type: single nucleotide variant
Location: chr2:178782990 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 972: the ig-like 3 domain

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 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-pro972 (accessed [today's date]).

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