Is AGK p.Arg137= (c.411A>T) pathogenic?

AGK p.Arg137= (c.411A>T) is classified Likely benign in AGK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-11). Very rare (popmax 0.0012%, sas); Associated with Sengers syndrome.

What condition is associated with AGK p.Arg137= (c.411A>T)?

AGK p.Arg137= (c.411A>T) is associated with Sengers syndrome, cataract 38 (ClinVar).

How common is AGK p.Arg137= (c.411A>T) in the general population?

AGK p.Arg137= (c.411A>T) is very rare (popmax 0.0012%, sas) (gnomAD).

AGK p.Arg137=

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.411A>T · rs1587129356 · VCV2937490

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0012%, sas)

Conditions

Sengers syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.3	GERP 5.4, phastCons 1
Overall
CADD	11.07	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0012% South Asian · 1/83,088 alleles

Overall 0.000144% 2/1,387,846 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0012%	83,088
European (non-Finnish)	8.83e-05%	1,132,516

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: AGK
Protein: p.Arg137=
Coding: c.411A>T
MANE Select: NM_018238
dbSNP: rs1587129356
Type: single nucleotide variant
Location: chr7:141614166 (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.Arg137fs Pathogenic ★ same residue
AGK c.1047-2A>T Pathogenic/Likely pathogenic ★★ same condition
AGK c.222-2A>C Likely pathogenic ★★ same condition
AGK c.297+2T>C Pathogenic ★★ same condition
AGK c.424-3C>G Pathogenic/Likely pathogenic ★★ same condition
AGK c.518+1G>A 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-arg137 (accessed [today's date]).

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