Is AMOT p.Arg120Gln (c.359G>A) pathogenic?

AMOT p.Arg120Gln (c.359G>A) is classified Uncertain significance in AMOT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-04). AlphaMissense: ambiguous (0.3953); Very rare (popmax 0.00261%, amr).

How common is AMOT p.Arg120Gln (c.359G>A) in the general population?

AMOT p.Arg120Gln (c.359G>A) is very rare (popmax 0.00261%, amr) (gnomAD).

What do computational predictors say about AMOT p.Arg120Gln (c.359G>A)?

AlphaMissense predicts ambiguous (score 0.3953) — an in-silico prediction, not a clinical call.

AMOT p.Arg120Gln

c.359G>A · VCV3536188

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3953 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00261%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3953	ambiguous
REVEL	0.197	benign-leaning
SaProt	LLR -5.51	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 470 bp · p 0.48 · regional, not allelic
Overall
CADD	26.7	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 0.00261% Admixed American · 1/38,299 alleles

Filtering AF 0.000676% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000494%

Overall 0.00112% 13/1,164,894 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00261%	38,299
African / African-American	0.00181%	55,342
European (non-Finnish)	0.00126%	79,331

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: AMOT
Protein: p.Arg120Gln
Coding: c.359G>A
MANE Select: NM_001113490
Type: single nucleotide variant
Location: chrX:112822768 (GRCh38)
Structure: AlphaFold pLDDT 58.16 · 18 PDB

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

Similar variants

AMOT p.Ala1032Val Benign ★★ same type
AMOT p.Ser316= Benign ★★ same type
AMOT p.Ser538= Benign ★★ same type
AMOT p.Ser780= Benign ★★ same type
AMOT p.Thr899Ala Benign ★★ same type
AMOT p.Gln642His Likely pathogenic ★ ⚠ same type
AMOT p.Ala1023Pro Uncertain significance ★ ⚠ same type
AMOT p.Ala460Gly 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/amot-p-arg120gln (accessed [today's date]).

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