Is AGMO p.Pro443Arg (c.1328C>G) pathogenic?

AGMO p.Pro443Arg (c.1328C>G) is classified Uncertain significance in AGMO (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-22). AlphaMissense: likely benign (0.0627); Very rare (popmax 0.0034%, nfe).

How common is AGMO p.Pro443Arg (c.1328C>G) in the general population?

AGMO p.Pro443Arg (c.1328C>G) is very rare (popmax 0.0034%, nfe) (gnomAD).

What do computational predictors say about AGMO p.Pro443Arg (c.1328C>G)?

AlphaMissense predicts likely benign (score 0.0627) — an in-silico prediction, not a clinical call.

AGMO p.Pro443Arg

c.1328C>G · rs769593390 · VCV3096076

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0627 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0034%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0627	likely benign
REVEL	0.05	moderately benign-leaning
SaProt	LLR -5.56	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.73	GERP -1.2, phastCons 0.087
Regional constraint	o/e 1.45	unconstrained · MANE · 361 kb · p 3.8e-25 · regional, not allelic
Overall
CADD	4.135	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0034% European (non-Finnish) · 40/1,177,856 alleles

Filtering AF 0.00256% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00273% 44/1,609,720 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0034%	29,446
Remaining individualsnot grpmax-eligible	0.00321%	31,148
African / African-American	0.00268%	37,383

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.Pro443Arg
Coding: c.1328C>G
MANE Select: NM_001004320
dbSNP: rs769593390
Type: single nucleotide variant
Location: chr7:15201295 (GRCh38)
Gene constraint: LOEUF 1.561 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.90

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-pro443arg (accessed [today's date]).

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