Is AGK p.Phe204Ser (c.611T>C) pathogenic?

AGK p.Phe204Ser (c.611T>C) is classified Uncertain significance in AGK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-18). AlphaMissense: likely pathogenic (0.9538); Very rare (popmax 0.00144%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AGK p.Phe204Ser (c.611T>C)?

AGK p.Phe204Ser (c.611T>C) is associated with Inborn genetic diseases (ClinVar).

How common is AGK p.Phe204Ser (c.611T>C) in the general population?

AGK p.Phe204Ser (c.611T>C) is very rare (popmax 0.00144%, nfe) (gnomAD).

What do computational predictors say about AGK p.Phe204Ser (c.611T>C)?

AlphaMissense predicts likely pathogenic (score 0.9538) — an in-silico prediction, not a clinical call.

AGK p.Phe204Ser

c.611T>C · rs1422298421 · VCV2487320

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9538 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00144%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9538	likely pathogenic · top 6% in AGK
REVEL	0.275	benign-leaning
SaProt	LLR -11.71	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	Δ0.23	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 5.2	GERP 5.3, phastCons 1
Overall
CADD	25.1	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 0.00144% European (non-Finnish) · 17/1,179,922 alleles

Filtering AF 0.000878% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000717%

Overall 0.0013% 19/1,461,744 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0032%	31,253
European (non-Finnish)grpmax	0.00144%	69,407

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Phe204Ser
Coding: c.611T>C
MANE Select: NM_018238
dbSNP: rs1422298421
Type: single nucleotide variant
Location: chr7:141633923 (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 204: 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

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-phe204ser (accessed [today's date]).

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