Is AGK p.Trp211Ter (c.632G>A) pathogenic?

AGK p.Trp211Ter (c.632G>A) is classified Pathogenic in AGK (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-19). Absent from gnomAD v4.1; Associated with cataract 38.

What condition is associated with AGK p.Trp211Ter (c.632G>A)?

AGK p.Trp211Ter (c.632G>A) is associated with cataract 38, Sengers syndrome (ClinVar).

How common is AGK p.Trp211Ter (c.632G>A) in the general population?

AGK p.Trp211Ter (c.632G>A) is absent from gnomAD v4.1 (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.Trp211Ter

c.632G>A · rs2116998520 · VCV1415657

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

cataract 38

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	Δ0.42	donor loss · deltas
Pangolin	Δ0.53	loss · gain 0.00 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 9.9	GERP 5.6, phastCons 1
Overall
CADD	41.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AGK
Protein: p.Trp211Ter
Coding: c.632G>A
MANE Select: NM_018238
dbSNP: rs2116998520
Type: single nucleotide variant
Location: chr7:141633944 (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 211: 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-trp211ter (accessed [today's date]).

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