Is AGMO p.Ala287Pro (c.859G>C) pathogenic?

AGMO p.Ala287Pro (c.859G>C) is classified Uncertain significance in AGMO (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-09). AlphaMissense: ambiguous (0.5365); Ultra-rare (popmax 0.0614%, afr).

How common is AGMO p.Ala287Pro (c.859G>C) in the general population?

AGMO p.Ala287Pro (c.859G>C) is ultra-rare (popmax 0.0614%, afr) (gnomAD).

What do computational predictors say about AGMO p.Ala287Pro (c.859G>C)?

AlphaMissense predicts ambiguous (score 0.5365) — an in-silico prediction, not a clinical call.

AGMO p.Ala287Pro

c.859G>C · VCV3507005

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5365 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0614%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5365	ambiguous
REVEL	0.185	benign-leaning
SaProt	LLR -13.50	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.97	GERP -2.7
Regional constraint	o/e 1.45	unconstrained · MANE · 361 kb · p 3.8e-25 · regional, not allelic
Overall
CADD	13.77	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

Grpmax group 0.0614% African / African-American · 46/74,858 alleles

Filtering AF 0.0473% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0423%

Overall 0.00335% 54/1,613,264 alleles · ultra-rare exomes 34/1,461,316 · genomes 20/151,948 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0614%	1,627
Middle Eastern	0.033%	3,027
Remaining individualsnot grpmax-eligible	0.0032%	31,232
European (non-Finnish)	0.000339%	294,897

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.Ala287Pro
Coding: c.859G>C
MANE Select: NM_001004320
Type: single nucleotide variant
Location: chr7:15387504 (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

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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-ala287pro (accessed [today's date]).

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