Is AMN1 p.Ser153Arg (c.457A>C) pathogenic?

AMN1 p.Ser153Arg (c.457A>C) is classified Uncertain significance in AMN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: likely benign (0.1648); Absent from gnomAD v4.1.

How common is AMN1 p.Ser153Arg (c.457A>C) in the general population?

AMN1 p.Ser153Arg (c.457A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMN1 p.Ser153Arg (c.457A>C)?

AlphaMissense predicts likely benign (score 0.1648) — an in-silico prediction, not a clinical call.

AMN1 p.Ser153Arg

c.457A>C · rs2497864150 · VCV3116081

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1648 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1648	likely benign
REVEL	0.099	moderately benign-leaning
SaProt	LLR -5.51	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.24	GERP -1.1
Regional constraint	o/e 0.80	unconstrained · MANE · 57 kb · p 0.00046 · regional, not allelic
Overall
CADD	11.77	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: AMN1
Protein: p.Ser153Arg
Coding: c.457A>C
MANE Select: NM_001113402
dbSNP: rs2497864150
Type: single nucleotide variant
Location: chr12:31697817 (GRCh38)
Gene constraint: LOEUF 0.838 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.56

Full AMN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMN1 p.Ala109Ser Uncertain significance ★ ⚠ same type
AMN1 p.Arg223Pro Uncertain significance ★ ⚠ same type
AMN1 p.Arg3Cys Uncertain significance ★ ⚠ same type
AMN1 p.Arg5Gln Uncertain significance ★ ⚠ same type
AMN1 p.Arg69Leu Uncertain significance ★ ⚠ same type
AMN1 p.Arg6Pro Uncertain significance ★ ⚠ same type
AMN1 p.Arg85Gly Uncertain significance ★ ⚠ same type
AMN1 p.Asn206Ser Uncertain significance ★ ⚠ same type

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/amn1-p-ser153arg (accessed [today's date]).

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