Is AGK p.Arg138Ter (c.412C>T) pathogenic?

AGK p.Arg138Ter (c.412C>T) is classified Pathogenic in AGK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-05). Very rare (popmax 0.00248%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AGK p.Arg138Ter (c.412C>T)?

AGK p.Arg138Ter (c.412C>T) is associated with Inborn genetic diseases, Sengers syndrome, cataract 38 (ClinVar).

How common is AGK p.Arg138Ter (c.412C>T) in the general population?

AGK p.Arg138Ter (c.412C>T) is very rare (popmax 0.00248%, nfe) (gnomAD).

AGK p.Arg138Ter

c.412C>T · rs1199705359 · VCV1351396

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00248%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function; NMD-escape possible for C-terminal truncations
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 4.2, phastCons 1
Overall
CADD	37.0	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

Grpmax group 0.00248% European (non-Finnish) · 28/1,130,232 alleles

Filtering AF 0.00172% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00148%

Overall 0.00195% 30/1,536,086 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00248%	40,365
Remaining individualsnot grpmax-eligible	0.00168%	59,384
South Asian	0.00121%	82,674

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.Arg138Ter
Coding: c.412C>T
MANE Select: NM_018238
dbSNP: rs1199705359
Type: single nucleotide variant
Location: chr7:141614167 (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 138: the dagkc domain; a UniProt-annotated variant site (in mtdps10)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Sengers syndrome cataract 38

Similar variants

AGK p.Arg138Gln 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
AGK c.518+1G>A Pathogenic ★★ same condition
AGK p.Arg137Ter 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-arg138ter (accessed [today's date]).

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