Is AGMO p.Pro183Ala (c.547C>G) pathogenic?

AGMO p.Pro183Ala (c.547C>G) is classified Uncertain significance in AGMO (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-27). AlphaMissense: likely benign (0.2806); Very rare (popmax 0.00737%, nfe).

How common is AGMO p.Pro183Ala (c.547C>G) in the general population?

AGMO p.Pro183Ala (c.547C>G) is very rare (popmax 0.00737%, nfe) (gnomAD).

What do computational predictors say about AGMO p.Pro183Ala (c.547C>G)?

AlphaMissense predicts likely benign (score 0.2806) — an in-silico prediction, not a clinical call.

AGMO p.Pro183Ala

c.547C>G · rs773104971 · VCV3096120

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2806 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00737%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2806	likely benign
REVEL	0.731	pathogenic-leaning
SaProt	LLR -11.78	damaging
⇒ REVEL and SaProt call this damaging; AlphaMissense does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 0.24, phastCons 1
Regional constraint	o/e 1.45	unconstrained · MANE · 361 kb · p 3.8e-25 · regional, not allelic
Overall
CADD	22.6	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 0.00737% European (non-Finnish) · 86/1,167,558 alleles

Filtering AF 0.0061% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00563%

Overall 0.00583% 92/1,577,428 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00822%	12,169
European (non-Finnish)grpmax	0.00737%	13,576
South Asian	0.00118%	84,988

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Pro183Ala
Coding: c.547C>G
MANE Select: NM_001004320
dbSNP: rs773104971
Type: single nucleotide variant
Location: chr7:15418620 (GRCh38)
Gene constraint: LOEUF 1.561 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.90
Residue 183: the fatty acid hydroxylase domain

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

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AGMO p.Leu213Val Uncertain significance ★★ ⚠ same type
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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-pro183ala (accessed [today's date]).

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