Is AGK p.Gly218= (c.654C>T) pathogenic?

AGK p.Gly218= (c.654C>T) is classified Likely benign in AGK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-04). Very rare (popmax 0.00668%, afr); Associated with cataract 38.

What condition is associated with AGK p.Gly218= (c.654C>T)?

AGK p.Gly218= (c.654C>T) is associated with cataract 38, Sengers syndrome (ClinVar).

How common is AGK p.Gly218= (c.654C>T) in the general population?

AGK p.Gly218= (c.654C>T) is very rare (popmax 0.00668%, 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.

AGK p.Gly218=

c.654C>T · rs144977618 · VCV2037995

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00668%, afr)

Conditions

cataract 38

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.37	donor loss · deltas
Pangolin	Δ0.22	loss · gain 0.01 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP -1.5	GERP 3.5
Overall
CADD	8.194	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00668% African / African-American · 5/74,858 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.00242% 39/1,613,448 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00668%	14,972
European (non-Finnish)	0.00271%	36,863
Finnishnot grpmax-eligible	0.00156%	63,988
South Asian	0.0011%	91,062

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.Gly218=
Coding: c.654C>T
MANE Select: NM_018238
dbSNP: rs144977618
Type: single nucleotide variant
Location: chr7:141633966 (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 218: a UniProt-annotated variant site (in mtdps10)

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-gly218 (accessed [today's date]).

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