Is AMT p.Arg62Trp (c.184C>T) pathogenic?

AMT p.Arg62Trp (c.184C>T) is classified Uncertain significance in AMT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2022-08-20). AlphaMissense: likely benign (0.145); Very rare (popmax 0.00333%, amr); Associated with Inborn genetic diseases.

What condition is associated with AMT p.Arg62Trp (c.184C>T)?

AMT p.Arg62Trp (c.184C>T) is associated with Inborn genetic diseases, glycine encephalopathy (ClinVar).

How common is AMT p.Arg62Trp (c.184C>T) in the general population?

AMT p.Arg62Trp (c.184C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about AMT p.Arg62Trp (c.184C>T)?

AlphaMissense predicts likely benign (score 0.145) — an in-silico prediction, not a clinical call.

AMT p.Arg62Trp

c.184C>T · rs779008890 · VCV2198317

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.145 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.145	likely benign
REVEL	0.425	indeterminate
SaProt	LLR -10.86	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.034, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,907 bp · p 0.12 · regional, not allelic
Overall
CADD	25.9	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 · 2/60,008 alleles

Filtering AF 0.000763% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000605%

Overall 0.00105% 17/1,613,870 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00333%	30,004
European (non-Finnish)	0.00127%	78,670

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: AMT
Protein: p.Arg62Trp
Coding: c.184C>T
MANE Select: NM_000481
dbSNP: rs779008890
Type: single nucleotide variant
Location: chr3:49422178 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66 · 2 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: glycine encephalopathy

Similar variants

AMT p.Arg62Gln Uncertain significance ★ ⚠ same residue
AMT p.Arg62= Likely benign ★ same residue
AMT c.339+2T>C Likely pathogenic ★★ same condition
AMT c.471+2T>C Pathogenic ★★ same condition
AMT c.697-1G>A Likely pathogenic ★★ same condition
AMT c.878-1G>A Pathogenic ★★ same condition
AMT c.91-2A>G Likely pathogenic ★★ same condition
AMT c.-58C>T Pathogenic/Likely pathogenic ★★ same condition

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/amt-p-arg62trp (accessed [today's date]).

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