Is AMN1 p.Val100Ile (c.298G>A) pathogenic?

AMN1 p.Val100Ile (c.298G>A) is classified Likely benign in AMN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-11). AlphaMissense: likely benign (0.0712); Very rare (popmax 0.00382%, nfe).

How common is AMN1 p.Val100Ile (c.298G>A) in the general population?

AMN1 p.Val100Ile (c.298G>A) is very rare (popmax 0.00382%, nfe) (gnomAD).

What do computational predictors say about AMN1 p.Val100Ile (c.298G>A)?

AlphaMissense predicts likely benign (score 0.0712) — an in-silico prediction, not a clinical call.

AMN1 p.Val100Ile

c.298G>A · VCV4640243

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0712 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00382%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0712	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -5.48	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 0.033	GERP -3.9, phastCons 0.68
Regional constraint	o/e 0.80	unconstrained · MANE · 57 kb · p 0.00046 · regional, not allelic
Overall
CADD	0.429	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 0.00382% European (non-Finnish) · 45/1,177,090 alleles

Filtering AF 0.00291% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0026%

Overall 0.00287% 46/1,601,824 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00382%	26,158
Remaining individualsnot grpmax-eligible	0.00161%	61,994

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: AMN1
Protein: p.Val100Ile
Coding: c.298G>A
MANE Select: NM_001113402
Type: single nucleotide variant
Location: chr12:31701881 (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-val100ile (accessed [today's date]).

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