Is TTN p.Ser9237Pro (c.27709T>C) pathogenic?

TTN p.Ser9237Pro (c.27709T>C) is classified Uncertain significance in TTN (ClinVar, Single submitter, 1 submitter; last evaluated 2019-04-30). AlphaMissense: likely pathogenic (0.9732); Absent from gnomAD v4.1; Associated with tibial muscular dystrophy.

What condition is associated with TTN p.Ser9237Pro (c.27709T>C)?

TTN p.Ser9237Pro (c.27709T>C) is associated with tibial muscular dystrophy (ClinVar).

How common is TTN p.Ser9237Pro (c.27709T>C) in the general population?

TTN p.Ser9237Pro (c.27709T>C) is absent from gnomAD v4.1 (gnomAD).

How is Tibial muscular dystrophy inherited?

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

What do computational predictors say about TTN p.Ser9237Pro (c.27709T>C)?

AlphaMissense predicts likely pathogenic (score 0.9732) — an in-silico prediction, not a clinical call.

TTN p.Ser9237Pro

c.27709T>C · rs766638714 · VCV932120

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9732 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

tibial muscular dystrophy

Computational evidence

Protein change
AlphaMissense	0.9732	likely pathogenic · top 8% in TTN
REVEL	0.639	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.8, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 141 kb · p 0.23 · regional, not allelic
Overall
CADD	23.1	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM S8920P vs ClinVar S9237P) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: TTN
Protein: p.Ser9237Pro
Coding: c.27709T>C
MANE Select: NM_001267550
dbSNP: rs766638714
Type: single nucleotide variant
Location: chr2:178712121 (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

tibial muscular dystrophy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Tibial muscular dystrophy (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Adult
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

TTN p.Ser9237= Likely benign ★★ same residue
TTN p.Ser9237Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
TTN c.107377+1G>A Pathogenic/Likely pathogenic ★★ same condition
TTN c.107377+1G>C Pathogenic/Likely pathogenic ★★ same condition
TTN c.2775+1G>T Likely pathogenic ★★ same condition
TTN c.39974-11T>G Pathogenic/Likely pathogenic ★★ same condition
TTN c.56051-1G>A Likely pathogenic ★★ same condition
TTN c.67349-2A>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-ser9237pro (accessed [today's date]).

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