Is AMER1 p.Pro128His (c.383C>A) pathogenic?

AMER1 p.Pro128His (c.383C>A) is classified Uncertain significance in AMER1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-07-22). AlphaMissense: likely benign (0.1115); Absent from gnomAD v4.1; Associated with AMER1-related disorder.

What condition is associated with AMER1 p.Pro128His (c.383C>A)?

AMER1 p.Pro128His (c.383C>A) is associated with AMER1-related disorder (ClinVar).

How common is AMER1 p.Pro128His (c.383C>A) in the general population?

AMER1 p.Pro128His (c.383C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMER1 p.Pro128His (c.383C>A)?

AlphaMissense predicts likely benign (score 0.1115) — an in-silico prediction, not a clinical call.

AMER1 p.Pro128His

c.383C>A · VCV3347397

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1115 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

AMER1-related disorder

Computational evidence

Protein change
AlphaMissense	0.1115	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -7.71	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 4.5	GERP 0.82, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 3,404 bp · p 0.037 · regional, not allelic
Overall
CADD	21.6	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

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: AMER1
Protein: p.Pro128His
Coding: c.383C>A
MANE Select: NM_152424
Type: single nucleotide variant
Location: chrX:64192904 (GRCh38)
Structure: AlphaFold pLDDT 48.88 · 3 PDB

Full AMER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

AMER1-related disorder

Similar variants

AMER1 p.Glu191Ter Pathogenic/Likely pathogenic ★★ same condition
AMER1 p.Cys125Ter Likely pathogenic ★ same condition
AMER1 p.Glu7Ter Likely pathogenic ★ same condition
AMER1 p.Ala610Gly Conflicting classifications of pathogenicity ★ ⚠ same condition
AMER1 p.Cys964Ser Uncertain significance ★ ⚠ same condition
AMER1 p.Leu69Met Conflicting classifications of pathogenicity ★ ⚠ same condition
AMER1 p.Ala992Thr Uncertain significance ⚠ same condition
AMER1 p.Arg646Gln 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/amer1-p-pro128his (accessed [today's date]).

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