Is AGMAT p.Arg34Cys (c.100C>T) pathogenic?

AGMAT p.Arg34Cys (c.100C>T) is classified Uncertain significance in AGMAT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely benign (0.1013); Ultra-rare (popmax 0.0383%, eas).

How common is AGMAT p.Arg34Cys (c.100C>T) in the general population?

AGMAT p.Arg34Cys (c.100C>T) is ultra-rare (popmax 0.0383%, eas) (gnomAD).

What do computational predictors say about AGMAT p.Arg34Cys (c.100C>T)?

AlphaMissense predicts likely benign (score 0.1013) — an in-silico prediction, not a clinical call.

AGMAT p.Arg34Cys

c.100C>T · rs566899293 · VCV2238958

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1013 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0383%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1013	likely benign
REVEL	0.187	benign-leaning
SaProt	LLR -8.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP -4.2, phastCons 0.99
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.99 · regional, not allelic
Overall
CADD	18.94	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.0383% East Asian · 13/33,978 alleles

Filtering AF 0.0225% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0179%

Overall 0.00113% 16/1,410,552 alleles · ultra-rare exomes 10/1,258,352 · genomes 6/152,200 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0383%	2,614
Remaining individualsnot grpmax-eligible	0.00186%	53,622
European (non-Finnish)	0.000184%	544,132

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.Arg34Cys
Coding: c.100C>T
MANE Select: NM_024758
dbSNP: rs566899293
Type: single nucleotide variant
Location: chr1:15584868 (GRCh38)
Gene constraint: LOEUF 1.712 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.12
Residue 34: the 'disordered' region

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

Similar variants

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
AGMAT p.Ala74Ser 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-arg34cys (accessed [today's date]).

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