Is AGK p.Arg9Gln (c.26G>A) pathogenic?

AGK p.Arg9Gln (c.26G>A) is classified Conflicting classifications of pathogenicity in AGK (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-19). AlphaMissense: likely benign (0.2076); Rare (popmax 0.936%, sas); Associated with cataract 38.

What condition is associated with AGK p.Arg9Gln (c.26G>A)?

AGK p.Arg9Gln (c.26G>A) is associated with cataract 38, Sengers syndrome (ClinVar).

How common is AGK p.Arg9Gln (c.26G>A) in the general population?

AGK p.Arg9Gln (c.26G>A) is rare (popmax 0.936%, sas) (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.Arg9Gln (c.26G>A)?

AlphaMissense predicts likely benign (score 0.2076) — an in-silico prediction, not a clinical call.

AGK p.Arg9Gln

c.26G>A · rs577821330 · VCV703559

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.2076 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.936%, sas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

cataract 38

Computational evidence

Protein change
AlphaMissense	0.2076	likely benign
REVEL	0.303	indeterminate
SaProt	LLR -10.00	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	Δ0.23	acceptor loss, 39 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 5.6	GERP 2.4, phastCons 1
Overall
CADD	26.0	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 0.936% South Asian · 852/91,012 alleles

Filtering AF 0.884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.863%

Overall 0.0587% 948/1,613,832 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.936%	107
Middle Eastern	0.0661%	1,514
Remaining individualsnot grpmax-eligible	0.064%	1,562
East Asian	0.00446%	22,428
African / African-American	0.004%	25,008
European (non-Finnish)	0.0039%	25,650
Admixed American	0.00167%	59,968

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.Arg9Gln
Coding: c.26G>A
MANE Select: NM_018238
dbSNP: rs577821330
Type: single nucleotide variant
Location: chr7:141555492 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.93 · 2 PDB

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 p.Arg9Pro Uncertain significance ★★ ⚠ same residue
AGK p.Arg9Ter Pathogenic ★ same residue
AGK p.Arg9= Uncertain significance ★ same residue
AGK p.Arg9Gly Uncertain significance ★ ⚠ 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

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-arg9gln (accessed [today's date]).

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