Is AGMO p.Phe198Ile (c.592T>A) pathogenic?

AGMO p.Phe198Ile (c.592T>A) is classified Uncertain significance in AGMO (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-13). AlphaMissense: likely pathogenic (0.9211); Very rare (popmax 8.55e-05%, nfe).

How common is AGMO p.Phe198Ile (c.592T>A) in the general population?

AGMO p.Phe198Ile (c.592T>A) is very rare (popmax 8.55e-05%, nfe) (gnomAD).

What do computational predictors say about AGMO p.Phe198Ile (c.592T>A)?

AlphaMissense predicts likely pathogenic (score 0.9211) — an in-silico prediction, not a clinical call.

AGMO p.Phe198Ile

c.592T>A · rs754148955 · VCV2411819

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9211 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.55e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9211	likely pathogenic · top 10% in AGMO
REVEL	0.869	moderately pathogenic-leaning
SaProt	LLR -13.09	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 0.56, phastCons 0.96
Regional constraint	o/e 1.45	unconstrained · MANE · 361 kb · p 3.8e-25 · regional, not allelic
Overall
CADD	23.9	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

Grpmax group 8.55e-05% European (non-Finnish) · 1/1,169,918 alleles

Overall 6.95e-05% 1/1,438,468 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: AGMO
Protein: p.Phe198Ile
Coding: c.592T>A
MANE Select: NM_001004320
dbSNP: rs754148955
Type: single nucleotide variant
Location: chr7:15418575 (GRCh38)
Gene constraint: LOEUF 1.561 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.90
Residue 198: the fatty acid hydroxylase domain

Full AGMO gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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AGMO p.Gly322Ser Uncertain significance ★★ ⚠ same type
AGMO p.Ile281Val Uncertain significance ★★ ⚠ same type
AGMO p.Leu213Val Uncertain significance ★★ ⚠ same type
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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/agmo-p-phe198ile (accessed [today's date]).

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