Is TCAP p.Glu5fs (c.14_15del) pathogenic?

TCAP p.Glu5fs (c.1415del) is classified Likely pathogenic in TCAP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-06-22). Very rare (popmax 0.00549%, sas); Associated with autosomal recessive limb-girdle muscular dystrophy type 2G.

What condition is associated with TCAP p.Glu5fs (c.14_15del)?

TCAP p.Glu5fs (c.14_15del) is associated with autosomal recessive limb-girdle muscular dystrophy type 2G (ClinVar).

How common is TCAP p.Glu5fs (c.14_15del) in the general population?

TCAP p.Glu5fs (c.14_15del) is very rare (popmax 0.00549%, sas) (gnomAD).

TCAP p.Glu5fs

Q: How is Telethonin-related limb-girdle muscular dystrophy R7 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.14_15del · rs757082868 · VCV1180772

Likely pathogenic Multiple submitters

Classification

Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00549%, sas)

Conditions

autosomal recessive limb-girdle muscular dystrophy type 2G

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 1 of 2
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.1	GERP 0.077, phastCons 0.001
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00549% South Asian · 5/91,084 alleles

Filtering AF 0.0021% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00136%

Overall 0.00031% 5/1,613,570 alleles · very rare exomes 4/1,461,466 · genomes 1/152,104 · joint denominator

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: TCAP
Protein: p.Glu5fs
Coding: c.14_15del
MANE Select: NM_003673
dbSNP: rs757082868
Type: Microsatellite
Location: chr17:39665371 (GRCh38)
Gene constraint: LOEUF 1.374 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.89 · 2 PDB
Residue 5: a β-strand

Full TCAP gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive limb-girdle muscular dystrophy type 2G — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Telethonin-related limb-girdle muscular dystrophy R7 (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent, Childhood, Infancy

Similar variants

TCAP p.Glu5Gly Uncertain significance ★ ⚠ same residue
TCAP p.Glu5Lys Uncertain significance ★ ⚠ same residue
TCAP c.110_110+1del Pathogenic ★★ same condition
TCAP c.110+5G>T Likely pathogenic ★★ same condition
TCAP p.Gln53Ter Pathogenic/Likely pathogenic ★★ same condition
TCAP p.Ser31fs Pathogenic/Likely pathogenic ★★ same condition
TCAP p.Trp22Ter Pathogenic/Likely pathogenic ★★ same condition
TCAP p.Trp25Ter 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/tcap-p-glu5fs (accessed [today's date]).

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