Is AMN p.Arg323Pro (c.968G>C) pathogenic?

AMN p.Arg323Pro (c.968G>C) is classified Uncertain significance in AMN (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-03). AlphaMissense: likely benign (0.2075); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with AMN p.Arg323Pro (c.968G>C)?

AMN p.Arg323Pro (c.968G>C) is associated with Inborn genetic diseases (ClinVar).

How common is AMN p.Arg323Pro (c.968G>C) in the general population?

AMN p.Arg323Pro (c.968G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMN p.Arg323Pro (c.968G>C)?

AlphaMissense predicts likely benign (score 0.2075) — an in-silico prediction, not a clinical call.

AMN p.Arg323Pro

c.968G>C · rs1248355711 · VCV2264407

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2075 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2075	likely benign
REVEL	0.43	indeterminate
SaProt	LLR -13.20	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.8	GERP -0.13, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 7,988 bp · p 0.14 · regional, not allelic
Overall
CADD	19.98	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

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: AMN
Protein: p.Arg323Pro
Coding: c.968G>C
MANE Select: NM_030943
dbSNP: rs1248355711
Type: single nucleotide variant
Location: chr14:102930048 (GRCh38)
Gene constraint: LOEUF 1.446 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 80.78 · 1 PDB
Residue 323: an α-helix

Full AMN 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

AMN p.Arg323Leu Uncertain significance ★ ⚠ same residue
AMN p.Arg323= Likely benign ★★ same residue
AMN p.Arg323Trp Uncertain significance ★ ⚠ same residue
AMN p.Ala238Thr Uncertain significance ★★ ⚠ same condition
AMN p.Ala44Thr Uncertain significance ★★ ⚠ same condition
AMN p.Arg271Trp Uncertain significance ★★ ⚠ same condition
AMN p.Arg424Gly Uncertain significance ★★ ⚠ same condition
AMN p.Cys250Trp 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/amn-p-arg323pro (accessed [today's date]).

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