Is AGMO p.Arg133Cys (c.397C>T) pathogenic?

AGMO p.Arg133Cys (c.397C>T) is classified Uncertain significance in AGMO (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-08-28). AlphaMissense: likely pathogenic (0.7399); Rare (popmax 0.206%, afr).

How common is AGMO p.Arg133Cys (c.397C>T) in the general population?

AGMO p.Arg133Cys (c.397C>T) is rare (popmax 0.206%, afr) (gnomAD).

What do computational predictors say about AGMO p.Arg133Cys (c.397C>T)?

AlphaMissense predicts likely pathogenic (score 0.7399) — an in-silico prediction, not a clinical call.

AGMO p.Arg133Cys

c.397C>T · rs149570873 · VCV1301491

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.7399 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.206%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7399	likely pathogenic
REVEL	0.916	moderately pathogenic-leaning
SaProt	LLR -15.16	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5	GERP 1.2, phastCons 1
Regional constraint	o/e 1.45	unconstrained · MANE · 361 kb · p 3.8e-25 · regional, not allelic
Overall
CADD	28.5	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 0.206% African / African-American · 153/74,376 alleles

Filtering AF 0.179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.169%

Overall 0.011% 175/1,597,572 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.206%	486
Middle Eastern	0.0167%	5,994
Remaining individualsnot grpmax-eligible	0.0146%	6,851
Admixed American	0.014%	7,139
South Asian	0.00114%	88,084
European (non-Finnish)	0.000256%	390,862

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.Arg133Cys
Coding: c.397C>T
MANE Select: NM_001004320
dbSNP: rs149570873
Type: single nucleotide variant
Location: chr7:15544784 (GRCh38)
Gene constraint: LOEUF 1.561 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.90
Residue 133: the fatty acid hydroxylase domain

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

Similar variants

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
AGMO p.Pro218Leu 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-arg133cys (accessed [today's date]).

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