Is AGK p.Phe4Cys (c.11T>G) pathogenic?

AGK p.Phe4Cys (c.11T>G) is classified Uncertain significance in AGK (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-22). AlphaMissense: likely benign (0.1594); Absent from gnomAD v4.1.

How common is AGK p.Phe4Cys (c.11T>G) in the general population?

AGK p.Phe4Cys (c.11T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGK p.Phe4Cys (c.11T>G)?

AlphaMissense predicts likely benign (score 0.1594) — an in-silico prediction, not a clinical call.

AGK p.Phe4Cys

c.11T>G · VCV3900481

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1594 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1594	likely benign
REVEL	0.204	benign-leaning
SaProt	LLR -9.00	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 5.9	GERP 3.2, phastCons 1
Overall
CADD	26.2	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

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.Phe4Cys
Coding: c.11T>G
MANE Select: NM_018238
Type: single nucleotide variant
Location: chr7:141555477 (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

Similar variants

AGK c.1047-2A>T Pathogenic/Likely pathogenic ★★ same type
AGK c.222-2A>C Likely pathogenic ★★ same type
AGK c.297+2T>C Pathogenic ★★ same type
AGK c.424-3C>G Pathogenic/Likely pathogenic ★★ same type
AGK c.518+1G>A Pathogenic ★★ same type
AGK p.Arg137Ter Pathogenic ★★ same type
AGK p.Arg138Ter Pathogenic ★★ same type
AGK p.Arg281Ter Pathogenic ★★ same type

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-phe4cys (accessed [today's date]).

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