Is AGMO p.Pro302Leu (c.905C>T) pathogenic?

AGMO p.Pro302Leu (c.905C>T) is classified Uncertain significance in AGMO (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-30). AlphaMissense: likely pathogenic (0.7991); Ultra-rare (popmax 0.035%, amr).

How common is AGMO p.Pro302Leu (c.905C>T) in the general population?

AGMO p.Pro302Leu (c.905C>T) is ultra-rare (popmax 0.035%, amr) (gnomAD).

What do computational predictors say about AGMO p.Pro302Leu (c.905C>T)?

AlphaMissense predicts likely pathogenic (score 0.7991) — an in-silico prediction, not a clinical call.

AGMO p.Pro302Leu

c.905C>T · rs751893917 · VCV2375858

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7991 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.035%, amr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7991	likely pathogenic
REVEL	0.734	pathogenic-leaning
SaProt	LLR -11.88	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.21	donor loss, 14 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 9.6	GERP 2.4, phastCons 1
Regional constraint	o/e 1.45	unconstrained · MANE · 361 kb · p 3.8e-25 · regional, not allelic
Overall
CADD	32.0	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 0.035% Admixed American · 21/60,006 alleles

Filtering AF 0.0234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0197%

Overall 0.00489% 79/1,613,912 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.035%	2,857
Remaining individualsnot grpmax-eligible	0.0096%	10,415
African / African-American	0.00934%	10,710
East Asian	0.00446%	22,435
European (non-Finnish)	0.00364%	27,440

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.Pro302Leu
Coding: c.905C>T
MANE Select: NM_001004320
dbSNP: rs751893917
Type: single nucleotide variant
Location: chr7:15387458 (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.Pro302Ser Uncertain significance ⚠ same residue
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

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-pro302leu (accessed [today's date]).

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