Is AMT p.Pro185= (c.555C>T) pathogenic?

AMT p.Pro185= (c.555C>T) is classified Likely benign in AMT (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-26). Ultra-rare (popmax 0.0308%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AMT p.Pro185= (c.555C>T)?

AMT p.Pro185= (c.555C>T) is associated with Inborn genetic diseases, glycine encephalopathy, glycine encephalopathy 1 (ClinVar).

How common is AMT p.Pro185= (c.555C>T) in the general population?

AMT p.Pro185= (c.555C>T) is ultra-rare (popmax 0.0308%, nfe) (gnomAD).

AMT p.Pro185=

c.555C>T · rs144790394 · VCV553783

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0308%, nfe)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.358	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.2	GERP -0.055, phastCons 1
Overall
CADD	10.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0308% European (non-Finnish) · 364/1,179,932 alleles

Filtering AF 0.0282% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0272%

Overall 0.0231% 373/1,613,740 alleles · ultra-rare exomes 363/1,461,546 · genomes 10/152,194 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0308%	3,242
Remaining individualsnot grpmax-eligible	0.00961%	10,409
African / African-American	0.00267%	37,457
Admixed American	0.00167%	59,938

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.Pro185=
Coding: c.555C>T
MANE Select: NM_000481
dbSNP: rs144790394
Type: single nucleotide variant
Location: chr3:49419401 (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 glycine encephalopathy 1

Similar variants

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
AMT p.Arg222Cys Pathogenic ★★ same condition
AMT p.Arg265Cys 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-pro185 (accessed [today's date]).

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