Is AGK p.Ala42Pro (c.124G>C) pathogenic?

AGK p.Ala42Pro (c.124G>C) is classified Uncertain significance in AGK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-17). AlphaMissense: likely pathogenic (0.9835); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AGK p.Ala42Pro (c.124G>C)?

AGK p.Ala42Pro (c.124G>C) is associated with Inborn genetic diseases (ClinVar).

How common is AGK p.Ala42Pro (c.124G>C) in the general population?

AGK p.Ala42Pro (c.124G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGK p.Ala42Pro (c.124G>C)?

AlphaMissense predicts likely pathogenic (score 0.9835) — an in-silico prediction, not a clinical call.

AGK p.Ala42Pro

c.124G>C · rs775499077 · VCV2430806

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9835 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9835	likely pathogenic · top 2% in AGK
REVEL	0.373	indeterminate
SaProt	LLR -15.08	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 4, phastCons 1
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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.Ala42Pro
Coding: c.124G>C
MANE Select: NM_018238
dbSNP: rs775499077
Type: single nucleotide variant
Location: chr7:141593168 (GRCh38)
Gene constraint: LOEUF 0.918 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.93 · 2 PDB

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.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
AGK p.Gly208Ser 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-ala42pro (accessed [today's date]).

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