Is AMOT p.Arg24Cys (c.70C>T) pathogenic?

AMOT p.Arg24Cys (c.70C>T) is classified Uncertain significance in AMOT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-07). AlphaMissense: likely pathogenic (0.8462); Very rare (popmax 0.000344%, nfe).

How common is AMOT p.Arg24Cys (c.70C>T) in the general population?

AMOT p.Arg24Cys (c.70C>T) is very rare (popmax 0.000344%, nfe) (gnomAD).

What do computational predictors say about AMOT p.Arg24Cys (c.70C>T)?

AlphaMissense predicts likely pathogenic (score 0.8462) — an in-silico prediction, not a clinical call.

AMOT p.Arg24Cys

c.70C>T · rs946043007 · VCV2281491

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8462 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000344%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8462	likely pathogenic
REVEL	0.371	indeterminate
SaProt	LLR -9.98	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 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 470 bp · p 0.48 · regional, not allelic
Overall
CADD	27.9	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 0.000344% European (non-Finnish) · 3/872,666 alleles

Filtering AF 9.2e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.5e-05%

Overall 0.000257% 3/1,165,605 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: AMOT
Protein: p.Arg24Cys
Coding: c.70C>T
MANE Select: NM_001113490
dbSNP: rs946043007
Type: single nucleotide variant
Location: chrX:112823057 (GRCh38)
Structure: AlphaFold pLDDT 58.16 · 18 PDB
Residue 24: the 'disordered' region

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

Similar variants

AMOT p.Arg24Gly Uncertain significance ★ ⚠ same residue
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

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-arg24cys (accessed [today's date]).

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