Is AGK c.*992G>A pathogenic?

AGK c.992G>A is classified Likely benign in AGK (ClinVar, Single submitter, 1 submitter; last evaluated 2018-01-12). Rare (popmax 0.275%, amr); Associated with cataract 38.

What condition is associated with AGK c.*992G>A?

AGK c.*992G>A is associated with cataract 38, Sengers syndrome (ClinVar).

How common is AGK c.*992G>A in the general population?

AGK c.*992G>A is rare (popmax 0.275%, amr) (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.

AGK c.*992G>A

rs191308473 · VCV359077

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.275%, amr)

Conditions

cataract 38

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 0.49	GERP 3.4, phastCons 0.12
Non-coding constraint	Z 4.00	1 kb window · o/e 0.72 · regional · uncalibrated
Overall
CADD	2.834	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.275% Admixed American · 42/15,300 alleles

Filtering AF 0.225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.213%

Overall 0.167% 255/152,242 alleles · rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.284%	352
Admixed Americangrpmax	0.275%	364
European (non-Finnish)	0.256%	391
African / African-American	0.065%	1,539
South Asian	0.0415%	2,409
Finnishnot grpmax-eligible	0.0283%	3,529
East Asian	0.0193%	5,186

Remaining individuals 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
Coding: c.*992G>A
MANE Select: NM_018238
dbSNP: rs191308473
Type: single nucleotide variant
Location: chr7:141653916 (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 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-c-star-992g-a (accessed [today's date]).

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