Is AGK p.Arg137fs (c.409del) pathogenic?

AGK p.Arg137fs (c.409del) is classified Pathogenic in AGK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). Absent from gnomAD; Associated with Sengers syndrome.

What condition is associated with AGK p.Arg137fs (c.409del)?

AGK p.Arg137fs (c.409del) is associated with Sengers syndrome, cataract 38 (ClinVar).

How common is AGK p.Arg137fs (c.409del) in the general population?

AGK p.Arg137fs (c.409del) is absent from gnomAD (gnomAD).

AGK p.Arg137fs

Q: How is Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome inherited?

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

c.409del · rs2485387302 · VCV2952828

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

Sengers syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.48	GERP 1.4, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AGK
Protein: p.Arg137fs
Coding: c.409del
MANE Select: NM_018238
dbSNP: rs2485387302
Type: Deletion
Location: chr7:141614164 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.93 · 2 PDB
Residue 137: the dagkc domain; a UniProt-annotated variant site (in mtdps10)

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

Disease context

Sengers syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cataract 38

For Congenital cataract-hypertrophic cardiomyopathy-mitochondrial myopathy syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

AGK p.Arg137Ter Pathogenic ★★ same residue
AGK p.Arg137Gln Uncertain significance ★★ ⚠ same residue
AGK p.Arg137= Likely benign ★ same residue
AGK p.Thr347_Ile348del Uncertain significance ★★ same condition
AGK c.424-3del Benign/Likely benign ★★ same condition
AGK c.519-4_519-3del Likely benign ★★ same condition
AGK p.Leu404_Lys412del Likely pathogenic ★ same condition
AGK p.Phe383_Ser384insTer 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/agk-p-arg137fs (accessed [today's date]).

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