Is AMOT p.Arg368His (c.1103G>A) pathogenic?

AMOT p.Arg368His (c.1103G>A) is classified Likely benign in AMOT (ClinVar, No assertion criteria, 2 submitters). AlphaMissense: likely benign (0.1196); Ultra-rare (popmax 0.0231%, mid).

How common is AMOT p.Arg368His (c.1103G>A) in the general population?

AMOT p.Arg368His (c.1103G>A) is ultra-rare (popmax 0.0231%, mid) (gnomAD).

What do computational predictors say about AMOT p.Arg368His (c.1103G>A)?

AlphaMissense predicts likely benign (score 0.1196) — an in-silico prediction, not a clinical call.

AMOT p.Arg368His

c.1103G>A · rs370543375 · VCV1206139

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1196 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0231%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1196	likely benign
REVEL	0.108	moderately benign-leaning
SaProt	LLR -6.72	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 4.7	GERP 0.27, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 18 kb · p 0.45 · regional, not allelic
Overall
CADD	24.2	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 0.0231% Middle Eastern · 1/4,328 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00392%

Overall 0.00522% 62/1,187,576 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0231%	4,328
South Asian	0.00915%	10,925
African / African-American	0.00711%	14,059
European (non-Finnish)	0.00565%	17,692
Ashkenazi Jewishnot grpmax-eligible	0.00461%	21,711
East Asian	0.00312%	32,056

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.Arg368His
Coding: c.1103G>A
MANE Select: NM_001113490
dbSNP: rs370543375
Type: single nucleotide variant
Location: chrX:112815647 (GRCh38)
Structure: AlphaFold pLDDT 58.16 · 18 PDB
Residue 368: the 'disordered' region

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

Similar variants

AMOT p.Arg368Cys 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-arg368his (accessed [today's date]).

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