Is AMT p.Ser77= (c.231G>A) pathogenic?

AMT p.Ser77= (c.231G>A) is classified Likely benign in AMT (ClinVar, Single submitter, 4 submitters; last evaluated 2026-01-04). Rare (popmax 0.135%, amr); Associated with glycine encephalopathy.

What condition is associated with AMT p.Ser77= (c.231G>A)?

AMT p.Ser77= (c.231G>A) is associated with glycine encephalopathy, glycine encephalopathy 1 (ClinVar).

How common is AMT p.Ser77= (c.231G>A) in the general population?

AMT p.Ser77= (c.231G>A) is rare (popmax 0.135%, amr) (gnomAD).

How is Glycine encephalopathy inherited?

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

AMT p.Ser77=

c.231G>A · rs779002947 · VCV554628

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.135%, amr)

Conditions

glycine encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.046	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -6.9	GERP -4.5
Overall
CADD	7.795	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.135% Admixed American · 81/60,004 alleles

Filtering AF 0.111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.102%

Overall 0.00614% 99/1,613,686 alleles · rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.135%	741
Remaining individualsnot grpmax-eligible	0.008%	12,497
East Asian	0.00223%	44,902
South Asian	0.0022%	45,546
European (non-Finnish)	0.000847%	118,004

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.Ser77=
Coding: c.231G>A
MANE Select: NM_000481
dbSNP: rs779002947
Type: single nucleotide variant
Location: chr3:49422131 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66 · 2 PDB
Residue 77: a β-strand

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

Also linked: glycine encephalopathy 1

For Glycine encephalopathy (Orphanet):

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

Similar variants

AMT p.Ser77Leu Pathogenic/Likely pathogenic ★★ same residue
AMT p.Ser77Ter Likely pathogenic ★ 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-ser77 (accessed [today's date]).

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