Is TTN p.Pro31085= (c.93255G>A) pathogenic?

TTN p.Pro31085= (c.93255G>A) is classified Conflicting classifications of pathogenicity in TTN (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-11-25). Ultra-rare (popmax 0.0334%, afr); Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Pro31085= (c.93255G>A)?

TTN p.Pro31085= (c.93255G>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How common is TTN p.Pro31085= (c.93255G>A) in the general population?

TTN p.Pro31085= (c.93255G>A) is ultra-rare (popmax 0.0334%, afr) (gnomAD).

TTN p.Pro31085=

c.93255G>A · rs372611171 · VCV501487

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0334%, afr)

Conditions

Cardiovascular phenotype

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP -2.9	GERP -5.9
Overall
CADD	0.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0334% African / African-American · 25/74,922 alleles

Filtering AF 0.0231% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.00613% 99/1,613,726 alleles · ultra-rare exomes 85/1,461,586 · genomes 14/152,140 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0334%	2,997
Remaining individualsnot grpmax-eligible	0.0128%	7,807
South Asian	0.011%	9,108
East Asian	0.00891%	11,222
European (non-Finnish)	0.00441%	22,689

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.Pro31085=
Coding: c.93255G>A
MANE Select: NM_001267550
dbSNP: rs372611171
Type: single nucleotide variant
Location: chr2:178548371 (GRCh38)

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

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-pro31085 (accessed [today's date]).

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