Is AGK p.Lys6Arg (c.17A>G) pathogenic?

AGK p.Lys6Arg (c.17A>G) is classified Benign/Likely benign in AGK (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). AlphaMissense: likely benign (0.0643); Rare (popmax 0.521%, afr); Associated with cataract 38.

What condition is associated with AGK p.Lys6Arg (c.17A>G)?

AGK p.Lys6Arg (c.17A>G) is associated with cataract 38, Sengers syndrome (ClinVar).

How common is AGK p.Lys6Arg (c.17A>G) in the general population?

AGK p.Lys6Arg (c.17A>G) is rare (popmax 0.521%, afr) (gnomAD).

How is Early onset non-syndromic cataract inherited?

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

What do computational predictors say about AGK p.Lys6Arg (c.17A>G)?

AlphaMissense predicts likely benign (score 0.0643) — an in-silico prediction, not a clinical call.

AGK p.Lys6Arg

c.17A>G · rs148294392 · VCV214064

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0643 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.521%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

cataract 38

Computational evidence

Protein change
AlphaMissense	0.0643	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -5.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.30 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.4	GERP 2.2, phastCons 1
Overall
CADD	14.78	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.521% African / African-American · 391/75,040 alleles

Filtering AF 0.478% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.462%

Overall 0.0924% 1,491/1,614,026 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.66%	60
African / African-Americangrpmax	0.521%	192
Remaining individualsnot grpmax-eligible	0.272%	368
Middle Eastern	0.198%	505
Admixed American	0.142%	706
European (non-Finnish)	0.0286%	3,501
Finnishnot grpmax-eligible	0.00468%	21,347
South Asian	0.0011%	91,048

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys6Arg
Coding: c.17A>G
MANE Select: NM_018238
dbSNP: rs148294392
Type: single nucleotide variant
Location: chr7:141555483 (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 6: a modified residue (n6-acetyllysine)

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

Disease context

cataract 38 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Sengers syndrome

For Early onset non-syndromic cataract (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive, X-linked recessive
Onset: Infancy, Neonatal

Similar variants

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
AGK p.Arg137Ter Pathogenic ★★ same condition
AGK p.Arg138Ter Pathogenic ★★ same condition
AGK p.Arg281Ter 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-lys6arg (accessed [today's date]).

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