Is AGMAT p.Arg243Trp (c.727C>T) pathogenic?

AGMAT p.Arg243Trp (c.727C>T) is classified Uncertain significance in AGMAT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). AlphaMissense: likely benign (0.1505); Very rare (popmax 0.00339%, nfe).

How common is AGMAT p.Arg243Trp (c.727C>T) in the general population?

AGMAT p.Arg243Trp (c.727C>T) is very rare (popmax 0.00339%, nfe) (gnomAD).

What do computational predictors say about AGMAT p.Arg243Trp (c.727C>T)?

AlphaMissense predicts likely benign (score 0.1505) — an in-silico prediction, not a clinical call.

AGMAT p.Arg243Trp

c.727C>T · rs138227623 · VCV2303177

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1505 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00339%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1505	likely benign
REVEL	0.8	moderately pathogenic-leaning
SaProt	LLR -10.36	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 6.6	GERP 2.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.99 · regional, not allelic
Overall
CADD	33.0	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 0.00339% European (non-Finnish) · 40/1,179,846 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00225%

Overall 0.00291% 47/1,613,722 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00339%	29,496
South Asian	0.00329%	30,351
East Asian	0.00223%	44,882
Admixed American	0.00167%	59,950
Remaining individualsnot grpmax-eligible	0.0016%	62,472
African / African-American	0.00133%	74,928

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.Arg243Trp
Coding: c.727C>T
MANE Select: NM_024758
dbSNP: rs138227623
Type: single nucleotide variant
Location: chr1:15577858 (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.Arg243Gln 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-arg243trp (accessed [today's date]).

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