Is AMT p.Ser234= (c.702G>A) pathogenic?

AMT p.Ser234= (c.702G>A) is classified Likely benign in AMT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-01). Very rare (popmax 0.00134%, afr); Associated with glycine encephalopathy.

What condition is associated with AMT p.Ser234= (c.702G>A)?

AMT p.Ser234= (c.702G>A) is associated with glycine encephalopathy (ClinVar).

How common is AMT p.Ser234= (c.702G>A) in the general population?

AMT p.Ser234= (c.702G>A) is very rare (popmax 0.00134%, afr) (gnomAD).

How is Glycine encephalopathy inherited?

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

AMT p.Ser234=

c.702G>A · rs761701860 · VCV1586736

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

glycine encephalopathy

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.17	moderately benign-leaning
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -9.8	GERP -4.2
Overall
CADD	0.556	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,874 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,613,812 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,874
European (non-Finnish)	0.000593%	168,566

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.Ser234=
Coding: c.702G>A
MANE Select: NM_000481
dbSNP: rs761701860
Type: single nucleotide variant
Location: chr3:49419146 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66 · 2 PDB
Residue 234: 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

For Glycine encephalopathy (Orphanet):

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

Similar variants

AMT p.Ser234Leu 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-ser234 (accessed [today's date]).

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