Is AGK p.Ser350Arg (c.1048A>C) pathogenic?

AGK p.Ser350Arg (c.1048A>C) is classified Uncertain significance in AGK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-01-19). AlphaMissense: likely pathogenic (0.5712); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AGK p.Ser350Arg (c.1048A>C)?

AGK p.Ser350Arg (c.1048A>C) is associated with Inborn genetic diseases, Sengers syndrome, cataract 38 (ClinVar).

How common is AGK p.Ser350Arg (c.1048A>C) in the general population?

AGK p.Ser350Arg (c.1048A>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about AGK p.Ser350Arg (c.1048A>C)?

AlphaMissense predicts likely pathogenic (score 0.5712) — an in-silico prediction, not a clinical call.

AGK p.Ser350Arg

c.1048A>C · rs863223894 · VCV2141246

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.5712 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5712	likely pathogenic
REVEL	0.194	benign-leaning
SaProt	LLR -6.81	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 5.6, phastCons 1
Overall
CADD	21.3	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 8.47e-05% European (non-Finnish) · 1/1,180,010 alleles

Overall 6.84e-05% 1/1,461,860 alleles · very rare

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.Ser350Arg
Coding: c.1048A>C
MANE Select: NM_018238
dbSNP: rs863223894
Type: single nucleotide variant
Location: chr7:141651526 (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 350: 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.Ser350Gly 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.Arg138Ter 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-ser350arg (accessed [today's date]).

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