Is TTN p.Pro30249= (c.90747T>C) pathogenic?

TTN p.Pro30249= (c.90747T>C) is classified Likely benign in TTN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-24). Very rare (popmax 0.005%, amr); Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Pro30249= (c.90747T>C)?

TTN p.Pro30249= (c.90747T>C) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How common is TTN p.Pro30249= (c.90747T>C) in the general population?

TTN p.Pro30249= (c.90747T>C) is very rare (popmax 0.005%, amr) (gnomAD).

TTN p.Pro30249=

c.90747T>C · rs765024828 · VCV1144998

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

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 -1.9	GERP -5.9
Overall
CADD	0.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,972 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00279% 45/1,613,686 alleles · very rare exomes 41/1,461,546 · genomes 4/152,140 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.101%	987
Remaining individualsnot grpmax-eligible	0.0112%	8,923
Admixed Americangrpmax	0.005%	19,991
European (non-Finnish)	0.000424%	235,960

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro30249=
Coding: c.90747T>C
MANE Select: NM_001267550
dbSNP: rs765024828
Type: single nucleotide variant
Location: chr2:178552153 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 30249: the fibronectin type-iii 120 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: dilated cardiomyopathy 1G autosomal recessive limb-girdle muscular dystrophy type 2J

Similar variants

TTN p.Pro30249Ala Likely benign ★ 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-pro30249 (accessed [today's date]).

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