Is TTN p.Ser8885= (c.26655C>T) pathogenic?

TTN p.Ser8885= (c.26655C>T) is classified Benign in TTN (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-02-04). Common (popmax 64.8%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Ser8885= (c.26655C>T)?

TTN p.Ser8885= (c.26655C>T) is associated with Cardiovascular phenotype, tibial muscular dystrophy, myopathy, myofibrillar, 9, with early respiratory failure (ClinVar).

TTN p.Ser8885=

Q: How common is TTN p.Ser8885= (c.26655C>T) in the general population?

TTN p.Ser8885= (c.26655C>T) is common (popmax 64.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.26655C>T · rs2562839 · VCV46784

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

gnomAD v4.1

Common

common (popmax 64.8%, eas) — too common for a highly-penetrant pathogenic allele

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 -0.77	GERP -4.1
Overall
CADD	7.401	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 64.8% East Asian · 29,033/44,792 alleles

Filtering AF 64.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 63.9%

Overall 24.7% 398,299/1,612,968 alleles · common exomes 351,913/1,461,024 · genomes 46,386/151,944 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	64.8%	2
Amishnot grpmax-eligible	54.4%	2
African / African-American	42.6%	2
South Asian	42%	2
Admixed American	39.7%	3
Middle Eastern	26.4%	4
Remaining individualsnot grpmax-eligible	26.3%	4
Finnishnot grpmax-eligible	20.4%	5
European (non-Finnish)	20.2%	5
Ashkenazi Jewishnot grpmax-eligible	20%	5

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.Ser8885=
Coding: c.26655C>T
MANE Select: NM_001267550
dbSNP: rs2562839
Type: single nucleotide variant
Location: chr2:178714003 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)

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 p.Ser8885Ala Uncertain significance ★ ⚠ same residue
TTN p.Ser8885Phe 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

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-ser8885 (accessed [today's date]).

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