Is AGK p.Met93Val (c.277A>G) pathogenic?

AGK p.Met93Val (c.277A>G) is classified Uncertain significance in AGK (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-28). AlphaMissense: likely benign (0.1544); Ultra-rare (popmax 0.0331%, mid); Associated with Inborn genetic diseases.

What condition is associated with AGK p.Met93Val (c.277A>G)?

AGK p.Met93Val (c.277A>G) is associated with Inborn genetic diseases (ClinVar).

How common is AGK p.Met93Val (c.277A>G) in the general population?

AGK p.Met93Val (c.277A>G) is ultra-rare (popmax 0.0331%, mid) (gnomAD).

What do computational predictors say about AGK p.Met93Val (c.277A>G)?

AlphaMissense predicts likely benign (score 0.1544) — an in-silico prediction, not a clinical call.

AGK p.Met93Val

c.277A>G · rs1373905406 · VCV2231180

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1544 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0331%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1544	likely benign
REVEL	0.192	benign-leaning
SaProt	LLR -6.85	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 3.8, phastCons 1
Overall
CADD	16.89	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0331% Middle Eastern · 2/6,050 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.000137% 2/1,460,664 alleles · ultra-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.Met93Val
Coding: c.277A>G
MANE Select: NM_018238
dbSNP: rs1373905406
Type: single nucleotide variant
Location: chr7:141601260 (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 93: the dagkc domain

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

Similar variants

AGK c.424-3C>G Pathogenic/Likely pathogenic ★★ same condition
AGK p.Arg138Ter Pathogenic ★★ same condition
AGK p.Ala42Pro Uncertain significance ★★ ⚠ same condition
AGK p.Ala71Val Uncertain significance ★★ ⚠ same condition
AGK p.Arg137Gln Uncertain significance ★★ ⚠ same condition
AGK p.Arg9Pro Uncertain significance ★★ ⚠ same condition
AGK p.Asn36Lys Uncertain significance ★★ ⚠ same condition
AGK p.Asn68Ser Uncertain significance ★★ ⚠ 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-met93val (accessed [today's date]).

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