Is AGMO p.Phe131Leu (c.393C>G) pathogenic?

AGMO p.Phe131Leu (c.393C>G) is classified Uncertain significance in AGMO (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-17). AlphaMissense: likely pathogenic (0.8457); Absent from gnomAD v4.1.

How common is AGMO p.Phe131Leu (c.393C>G) in the general population?

AGMO p.Phe131Leu (c.393C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AGMO p.Phe131Leu (c.393C>G)?

AlphaMissense predicts likely pathogenic (score 0.8457) — an in-silico prediction, not a clinical call.

AGMO p.Phe131Leu

c.393C>G · VCV3842502

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8457 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8457	likely pathogenic
REVEL	0.406	indeterminate
SaProt	LLR -4.54	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.5	GERP -2.3, phastCons 1
Regional constraint	o/e 1.45	unconstrained · MANE · 361 kb · p 3.8e-25 · regional, not allelic
Overall
CADD	17.32	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

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: AGMO
Protein: p.Phe131Leu
Coding: c.393C>G
MANE Select: NM_001004320
Type: single nucleotide variant
Location: chr7:15544788 (GRCh38)
Gene constraint: LOEUF 1.561 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.90
Residue 131: the fatty acid hydroxylase domain

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

Similar variants

AGMO p.Arg133Cys Uncertain significance ★★ ⚠ same type
AGMO p.Arg83Gln Uncertain significance ★★ ⚠ same type
AGMO p.Gly238Cys Uncertain significance ★★ ⚠ same type
AGMO p.Gly322Ser Uncertain significance ★★ ⚠ same type
AGMO p.Ile281Val Uncertain significance ★★ ⚠ same type
AGMO p.Leu213Val Uncertain significance ★★ ⚠ same type
AGMO p.Lys234Arg Uncertain significance ★★ ⚠ same type
AGMO p.Lys24Glu Uncertain significance ★★ ⚠ 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/agmo-p-phe131leu (accessed [today's date]).

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