Is AMT p.Leu155Phe (c.463C>T) pathogenic?

AMT p.Leu155Phe (c.463C>T) is classified Conflicting classifications of pathogenicity in AMT (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2026-01-05). AlphaMissense: likely benign (0.1295); Very rare (popmax 0.00856%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AMT p.Leu155Phe (c.463C>T)?

AMT p.Leu155Phe (c.463C>T) is associated with Inborn genetic diseases, glycine encephalopathy (ClinVar).

How common is AMT p.Leu155Phe (c.463C>T) in the general population?

AMT p.Leu155Phe (c.463C>T) is very rare (popmax 0.00856%, nfe) (gnomAD).

What do computational predictors say about AMT p.Leu155Phe (c.463C>T)?

AlphaMissense predicts likely benign (score 0.1295) — an in-silico prediction, not a clinical call.

AMT p.Leu155Phe

c.463C>T · rs201233398 · VCV1636183

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1295 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00856%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1295	likely benign
REVEL	0.252	benign-leaning
SaProt	LLR -7.82	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 10	GERP 2.2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,907 bp · p 0.12 · regional, not allelic
Overall
CADD	21.1	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 0.00856% European (non-Finnish) · 101/1,179,964 alleles

Filtering AF 0.00716% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00668%

Overall 0.00688% 111/1,613,988 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00856%	11,683
Remaining individualsnot grpmax-eligible	0.0048%	20,830
African / African-American	0.004%	24,974
Admixed American	0.00333%	29,998
South Asian	0.0022%	45,546

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.Leu155Phe
Coding: c.463C>T
MANE Select: NM_000481
dbSNP: rs201233398
Type: single nucleotide variant
Location: chr3:49420219 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66 · 2 PDB
Residue 155: an α-helix

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.Leu155Arg Uncertain significance ★ 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-leu155phe (accessed [today's date]).

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