Is AMT p.Pro354Ser (c.1060C>T) pathogenic?

AMT p.Pro354Ser (c.1060C>T) is classified Uncertain significance in AMT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-25). AlphaMissense: likely pathogenic (0.7103); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AMT p.Pro354Ser (c.1060C>T)?

AMT p.Pro354Ser (c.1060C>T) is associated with Inborn genetic diseases (ClinVar).

How common is AMT p.Pro354Ser (c.1060C>T) in the general population?

AMT p.Pro354Ser (c.1060C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMT p.Pro354Ser (c.1060C>T)?

AlphaMissense predicts likely pathogenic (score 0.7103) — an in-silico prediction, not a clinical call.

AMT p.Pro354Ser

c.1060C>T · rs2471145488 · VCV3117026

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7103 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.7103	likely pathogenic
REVEL	0.876	moderately pathogenic-leaning
SaProt	LLR -12.57	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 4,907 bp · p 0.12 · regional, not allelic
Overall
CADD	30.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AMT
Protein: p.Pro354Ser
Coding: c.1060C>T
MANE Select: NM_000481
dbSNP: rs2471145488
Type: single nucleotide variant
Location: chr3:49417692 (GRCh38)
Gene constraint: LOEUF 0.805 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.66 · 2 PDB
Residue 354: a turn

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

Similar variants

AMT p.Pro354= Likely benign ★ same residue
AMT p.Ala361Val Uncertain significance ★★ ⚠ same condition
AMT p.Arg10Gly Uncertain significance ★★ ⚠ same condition
AMT p.Arg219Cys Uncertain significance ★★ ⚠ same condition
AMT p.Arg297Gln Uncertain significance ★★ ⚠ same condition
AMT p.Arg34Cys Uncertain significance ★★ ⚠ same condition
AMT p.Arg381Gln Uncertain significance ★★ ⚠ same condition
AMT p.Arg62Trp Uncertain significance ★★ ⚠ 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-pro354ser (accessed [today's date]).

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