Is AMT p.Pro310Ser (c.928C>T) pathogenic?

AMT p.Pro310Ser (c.928C>T) is classified Uncertain significance in AMT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-24). AlphaMissense: likely benign (0.1006); Very rare (popmax 0.004%, afr); Associated with glycine encephalopathy.

What condition is associated with AMT p.Pro310Ser (c.928C>T)?

AMT p.Pro310Ser (c.928C>T) is associated with glycine encephalopathy (ClinVar).

How common is AMT p.Pro310Ser (c.928C>T) in the general population?

AMT p.Pro310Ser (c.928C>T) is very rare (popmax 0.004%, afr) (gnomAD).

How is Glycine encephalopathy inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about AMT p.Pro310Ser (c.928C>T)?

AlphaMissense predicts likely benign (score 0.1006) — an in-silico prediction, not a clinical call.

AMT p.Pro310Ser

c.928C>T · rs376165517 · VCV1960271

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1006 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

glycine encephalopathy

Computational evidence

Protein change
AlphaMissense	0.1006	likely benign
REVEL	0.233	benign-leaning
SaProt	LLR -9.41	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 3.3	GERP -1.1, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,907 bp · p 0.12 · regional, not allelic
Overall
CADD	15.42	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 0.004% African / African-American · 3/75,034 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.000205% 3/1,461,706 alleles · very rare

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.Pro310Ser
Coding: c.928C>T
MANE Select: NM_000481
dbSNP: rs376165517
Type: single nucleotide variant
Location: chr3:49417923 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66 · 2 PDB
Residue 310: an α-helix

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

Disease context

glycine encephalopathy — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Glycine encephalopathy (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

AMT p.Pro310= 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
AMT p.Arg222Cys 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-pro310ser (accessed [today's date]).

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