Is TTN p.Pro3238= (c.9714G>A) pathogenic?

TTN p.Pro3238= (c.9714G>A) is classified Conflicting classifications of pathogenicity in TTN (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-04-29). Very rare (popmax 0.00333%, amr); Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Pro3238= (c.9714G>A)?

TTN p.Pro3238= (c.9714G>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How common is TTN p.Pro3238= (c.9714G>A) in the general population?

TTN p.Pro3238= (c.9714G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

TTN p.Pro3238=

c.9714G>A · rs886042397 · VCV282437

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -10	GERP -5.3
Overall
CADD	3.844	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/59,976 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000207%

Overall 0.000616% 9/1,460,866 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	29,988
Remaining individualsnot grpmax-eligible	0.0016%	62,422
European (non-Finnish)	0.000509%	196,637

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.Pro3238=
Coding: c.9714G>A
MANE Select: NM_001267550
dbSNP: rs886042397
Type: single nucleotide variant
Location: chr2:178764801 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 3238: a UniProt-annotated variant site (in a bladder carcinoma sample; somatic mutation)

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.Pro3238Leu Conflicting classifications of pathogenicity ★ 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-pro3238 (accessed [today's date]).

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