Is TTN p.Ser31997= (c.95991C>T) pathogenic?

TTN p.Ser31997= (c.95991C>T) is classified Likely benign in TTN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-12). Ultra-rare (popmax 0.0227%, afr); Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Ser31997= (c.95991C>T)?

TTN p.Ser31997= (c.95991C>T) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How common is TTN p.Ser31997= (c.95991C>T) in the general population?

TTN p.Ser31997= (c.95991C>T) is ultra-rare (popmax 0.0227%, afr) (gnomAD).

TTN p.Ser31997=

c.95991C>T · rs375176758 · VCV413229

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0227%, afr)

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 · G>C here scores Δ0.33 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.9	GERP -5.9
Overall
CADD	0.013	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0227% African / African-American · 17/75,000 alleles

Filtering AF 0.0144% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0118%

Overall 0.00236% 38/1,613,564 alleles · ultra-rare exomes 23/1,461,366 · genomes 15/152,198 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0227%	4,412
South Asian	0.00329%	30,357
Remaining individualsnot grpmax-eligible	0.0016%	62,464
European (non-Finnish)	0.00144%	69,390

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.Ser31997=
Coding: c.95991C>T
MANE Select: NM_001267550
dbSNP: rs375176758
Type: single nucleotide variant
Location: chr2:178544238 (GRCh38)
Gene constraint: LOEUF 0.479 · pLI <0.01 · ClinGen HI 2/3 (gnomAD)
Residue 31997: a β-strand; the ig-like 142 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.Ser31997Gly Uncertain significance ★ 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-ser31997 (accessed [today's date]).

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