Is AGMO p.Ile232Lys (c.695T>A) pathogenic?

AGMO p.Ile232Lys (c.695T>A) is classified Uncertain significance in AGMO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-03). AlphaMissense: likely pathogenic (0.8407); Ultra-rare (popmax 0.0102%, amr).

How common is AGMO p.Ile232Lys (c.695T>A) in the general population?

AGMO p.Ile232Lys (c.695T>A) is ultra-rare (popmax 0.0102%, amr) (gnomAD).

What do computational predictors say about AGMO p.Ile232Lys (c.695T>A)?

AlphaMissense predicts likely pathogenic (score 0.8407) — an in-silico prediction, not a clinical call.

AGMO p.Ile232Lys

c.695T>A · VCV3842523

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8407 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0102%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8407	likely pathogenic
REVEL	0.578	indeterminate
SaProt	LLR -13.09	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 8	GERP 1.4, phastCons 1
Regional constraint	o/e 1.45	unconstrained · MANE · 361 kb · p 3.8e-25 · regional, not allelic
Overall
CADD	27.6	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 0.0102% Admixed American · 6/59,020 alleles

Filtering AF 0.00434% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00299%

Overall 0.000483% 7/1,449,858 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0102%	9,837
European (non-Finnish)	8.52e-05%	1,173,600

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.Ile232Lys
Coding: c.695T>A
MANE Select: NM_001004320
Type: single nucleotide variant
Location: chr7:15390887 (GRCh38)
Gene constraint: LOEUF 1.561 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.90
Residue 232: 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-ile232lys (accessed [today's date]).

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