Is TTN p.Pro23948= (c.71844T>C) pathogenic?

TTN p.Pro23948= (c.71844T>C) is classified Likely benign in TTN (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-08). Very rare (popmax 0.00668%, afr); Associated with Cardiovascular phenotype.

What condition is associated with TTN p.Pro23948= (c.71844T>C)?

TTN p.Pro23948= (c.71844T>C) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1G, autosomal recessive limb-girdle muscular dystrophy type 2J (ClinVar).

How common is TTN p.Pro23948= (c.71844T>C) in the general population?

TTN p.Pro23948= (c.71844T>C) is very rare (popmax 0.00668%, afr) (gnomAD).

TTN p.Pro23948=

c.71844T>C · rs750583121 · VCV512643

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00668%, 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 0.51	GERP -3.1, phastCons 0.81
Overall
CADD	0.365	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,896 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00162%

Overall 0.000496% 8/1,613,238 alleles · very rare exomes 1/1,461,118 · genomes 7/152,120 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,979
European (non-Finnish)	0.000254%	393,191

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.Pro23948=
Coding: c.71844T>C
MANE Select: NM_001267550
dbSNP: rs750583121
Type: single nucleotide variant
Location: chr2:178574288 (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-pro23948 (accessed [today's date]).

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