Is AGMAT p.Arg225Trp (c.673C>T) pathogenic?

AGMAT p.Arg225Trp (c.673C>T) is classified Uncertain significance in AGMAT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-14). AlphaMissense: ambiguous (0.3689); Very rare (popmax 0.00333%, amr).

How common is AGMAT p.Arg225Trp (c.673C>T) in the general population?

AGMAT p.Arg225Trp (c.673C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about AGMAT p.Arg225Trp (c.673C>T)?

AlphaMissense predicts ambiguous (score 0.3689) — an in-silico prediction, not a clinical call.

AGMAT p.Arg225Trp

c.673C>T · VCV4024341

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3689 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3689	ambiguous
REVEL	0.883	moderately pathogenic-leaning
SaProt	LLR -16.16	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.3	GERP 1.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.99 · regional, not allelic
Overall
CADD	31.0	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 0.00333% Admixed American · 2/60,016 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000681% 11/1,614,098 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,008
East Asian	0.00223%	44,872
European (non-Finnish)	0.000678%	147,503

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: AGMAT
Protein: p.Arg225Trp
Coding: c.673C>T
MANE Select: NM_024758
Type: single nucleotide variant
Location: chr1:15578906 (GRCh38)
Gene constraint: LOEUF 1.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.12

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

Similar variants

AGMAT p.Arg225Gln Uncertain significance ★ ⚠ same residue
AGMAT p.Thr229Met Benign ★★ same type
AGMAT p.Thr351= Benign ★★ same type
AGMAT p.Ala10Ser Uncertain significance ★ ⚠ same type
AGMAT p.Ala113Asp Uncertain significance ★ ⚠ same type
AGMAT p.Ala186Val Uncertain significance ★ ⚠ same type
AGMAT p.Ala285Val Uncertain significance ★ ⚠ same type
AGMAT p.Ala335Val 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/agmat-p-arg225trp (accessed [today's date]).

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