Is AMN p.Arg171Pro (c.512G>C) pathogenic?

AMN p.Arg171Pro (c.512G>C) is classified Uncertain significance in AMN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-20). AlphaMissense: ambiguous (0.452); Very rare (popmax 8.48e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with AMN p.Arg171Pro (c.512G>C)?

AMN p.Arg171Pro (c.512G>C) is associated with Inborn genetic diseases (ClinVar).

How common is AMN p.Arg171Pro (c.512G>C) in the general population?

AMN p.Arg171Pro (c.512G>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about AMN p.Arg171Pro (c.512G>C)?

AlphaMissense predicts ambiguous (score 0.452) — an in-silico prediction, not a clinical call.

AMN p.Arg171Pro

c.512G>C · VCV3293053

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.452 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.452	ambiguous
REVEL	0.221	benign-leaning
SaProt	LLR -13.94	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>A here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP 1.7	GERP -2.2, phastCons 1
Regional constraint	o/e 1.06	unconstrained · MANE · 7,988 bp · p 0.14 · regional, not allelic
Overall
CADD	20.7	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,338 alleles

Overall 6.92e-05% 1/1,445,976 alleles · very rare

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: AMN
Protein: p.Arg171Pro
Coding: c.512G>C
MANE Select: NM_030943
Type: single nucleotide variant
Location: chr14:102928974 (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 171: a disulfide bond; a β-strand

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.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
AMN p.Gln288His Uncertain significance ★★ ⚠ same condition
AMN p.Pro444Ser Uncertain significance ★★ ⚠ same condition
AMN p.Ser437Asn 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-arg171pro (accessed [today's date]).

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