Is AMN1 p.Trp255Arg (c.763T>C) pathogenic?

AMN1 p.Trp255Arg (c.763T>C) is classified Uncertain significance in AMN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-19). AlphaMissense: likely pathogenic (0.989); Absent from gnomAD v4.1.

How common is AMN1 p.Trp255Arg (c.763T>C) in the general population?

AMN1 p.Trp255Arg (c.763T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMN1 p.Trp255Arg (c.763T>C)?

AlphaMissense predicts likely pathogenic (score 0.989) — an in-silico prediction, not a clinical call.

AMN1 p.Trp255Arg

c.763T>C · VCV3861440

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.989 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,576,382)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.989	likely pathogenic · top 1% in AMN1
REVEL	0.52	indeterminate
SaProt	LLR -5.39	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 57 kb · p 0.00046 · regional, not allelic
Overall
CADD	26.6	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

No allele count reported in gnomAD v4.1 (AN 1,576,382). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: AMN1
Protein: p.Trp255Arg
Coding: c.763T>C
MANE Select: NM_001113402
Type: single nucleotide variant
Location: chr12:31672318 (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-trp255arg (accessed [today's date]).

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