Is AMOT p.Arg1064Ser (c.3192A>C) pathogenic?

AMOT p.Arg1064Ser (c.3192A>C) is classified Uncertain significance in AMOT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-13). AlphaMissense: ambiguous (0.4694); Very rare (popmax 0.00591%, eas).

How common is AMOT p.Arg1064Ser (c.3192A>C) in the general population?

AMOT p.Arg1064Ser (c.3192A>C) is very rare (popmax 0.00591%, eas) (gnomAD).

What do computational predictors say about AMOT p.Arg1064Ser (c.3192A>C)?

AlphaMissense predicts ambiguous (score 0.4694) — an in-silico prediction, not a clinical call.

AMOT p.Arg1064Ser

c.3192A>C · rs768392343 · VCV2623048

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4694 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00591%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4694	ambiguous
REVEL	0.289	benign-leaning
SaProt	LLR -7.56	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 1.2	GERP -2.8, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 12 kb · p 0.066 · regional, not allelic
Overall
CADD	18.97	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 0.00591% East Asian · 2/33,830 alleles

Filtering AF 0.000979% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000183% 2/1,094,382 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.Arg1064Ser
Coding: c.3192A>C
MANE Select: NM_001113490
dbSNP: rs768392343
Type: single nucleotide variant
Location: chrX:112778630 (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.Arg1064Gly 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-arg1064ser (accessed [today's date]).

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