Is TTN p.Ser3263= (c.9789C>T) pathogenic?

TTN p.Ser3263= (c.9789C>T) is classified Benign/Likely benign in TTN (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-04-10). Rare (popmax 0.1%, afr); Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Ser3263= (c.9789C>T)?

TTN p.Ser3263= (c.9789C>T) is associated with Cardiovascular phenotype, tibial muscular dystrophy, myopathy, myofibrillar, 9, with early respiratory failure (ClinVar).

How common is TTN p.Ser3263= (c.9789C>T) in the general population?

TTN p.Ser3263= (c.9789C>T) is rare (popmax 0.1%, afr) (gnomAD).

TTN p.Ser3263=

c.9789C>T · rs138313387 · VCV137830

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

gnomAD v4.1

Rare

rare (popmax 0.1%, afr)

Conditions

Cardiovascular phenotype

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 -9.1	GERP -5.3
Overall
CADD	0.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.1% African / African-American · 75/74,882 alleles

Filtering AF 0.0819% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0752%

Overall 0.00694% 112/1,613,932 alleles · rare exomes 59/1,461,802 · genomes 53/152,130 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.1%	998
Admixed American	0.01%	9,999
Remaining individualsnot grpmax-eligible	0.008%	12,497
European (non-Finnish)	0.00212%	47,200
South Asian	0.0011%	91,078

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.Ser3263=
Coding: c.9789C>T
MANE Select: NM_001267550
dbSNP: rs138313387
Type: single nucleotide variant
Location: chr2:178764726 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 3263: the ig-like 19 domain

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: 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

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-ser3263 (accessed [today's date]).

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