Is TTN p.Pro35896= (c.107688G>A) pathogenic?

TTN p.Pro35896= (c.107688G>A) is classified Benign/Likely benign in TTN (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-05-01). Ultra-rare (popmax 0.0719%, eas); Associated with hypertrophic cardiomyopathy 9.

What condition is associated with TTN p.Pro35896= (c.107688G>A)?

TTN p.Pro35896= (c.107688G>A) is associated with hypertrophic cardiomyopathy 9, tibial muscular dystrophy, myopathy, myofibrillar, 9, with early respiratory failure (ClinVar).

How common is TTN p.Pro35896= (c.107688G>A) in the general population?

TTN p.Pro35896= (c.107688G>A) is ultra-rare (popmax 0.0719%, eas) (gnomAD).

TTN p.Pro35896=

c.107688G>A · rs542575761 · VCV220650

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0719%, eas)

Conditions

hypertrophic cardiomyopathy 9

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 -0.014	GERP -4.7, phastCons 0.93
Overall
CADD	0.122	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0719% East Asian · 32/44,536 alleles

Filtering AF 0.0523% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0456%

Overall 0.00447% 71/1,589,870 alleles · ultra-rare exomes 57/1,437,706 · genomes 14/152,164 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0719%	1,392
Remaining individualsnot grpmax-eligible	0.0163%	6,134
Admixed American	0.00711%	14,058
African / African-American	0.00271%	36,890
South Asian	0.00229%	43,736
European (non-Finnish)	0.0018%	55,601

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.Pro35896=
Coding: c.107688G>A
MANE Select: NM_001267550
dbSNP: rs542575761
Type: single nucleotide variant
Location: chr2:178527300 (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

hypertrophic cardiomyopathy 9 — 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 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
TTN c.107377+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-pro35896 (accessed [today's date]).

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