Is AGK p.Phe406fs (c.1215dup) pathogenic?

AGK p.Phe406fs (c.1215dup) is classified Likely pathogenic in AGK (ClinVar, No assertion criteria, 1 submitter; last evaluated 2016-04-07). Absent from gnomAD; Associated with Sengers syndrome.

What condition is associated with AGK p.Phe406fs (c.1215dup)?

AGK p.Phe406fs (c.1215dup) is associated with Sengers syndrome (ClinVar).

How common is AGK p.Phe406fs (c.1215dup) in the general population?

AGK p.Phe406fs (c.1215dup) is absent from gnomAD (gnomAD).

AGK p.Phe406fs

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.1215dup · rs1587181981 · VCV617460

Likely pathogenic No assertion criteria

Classification

Likely pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

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 0.089	GERP 1.5, phastCons 0.003
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

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.Phe406fs
Coding: c.1215dup
MANE Select: NM_018238
dbSNP: rs1587181981
Type: Duplication
Location: chr7:141652869 (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 406: 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

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

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal

Similar variants

AGK p.Ser382fs Pathogenic/Likely pathogenic ★★ same condition
AGK c.424-3dup Benign/Likely benign ★★ same condition
AGK c.1046_1046+1dup Pathogenic ★ same condition
AGK p.Ile120fs Pathogenic ★ same condition
AGK p.Ile346fs Pathogenic ★ same condition
AGK p.Ile348fs Pathogenic ★ same condition
AGK p.Tyr390fs Pathogenic ★ same condition
AGK c.101+4_101+7dup Likely benign ★ 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-phe406fs (accessed [today's date]).

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