Is AMOT p.Asn445Ser (c.1334A>G) pathogenic?

AMOT p.Asn445Ser (c.1334A>G) is classified Uncertain significance in AMOT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-29). AlphaMissense: likely pathogenic (0.9804); Ultra-rare (popmax 0.0197%, amr).

How common is AMOT p.Asn445Ser (c.1334A>G) in the general population?

AMOT p.Asn445Ser (c.1334A>G) is ultra-rare (popmax 0.0197%, amr) (gnomAD).

What do computational predictors say about AMOT p.Asn445Ser (c.1334A>G)?

AlphaMissense predicts likely pathogenic (score 0.9804) — an in-silico prediction, not a clinical call.

AMOT p.Asn445Ser

c.1334A>G · rs964738689 · VCV3116119

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9804 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0197%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9804	likely pathogenic · top 8% in AMOT
REVEL	0.342	indeterminate
SaProt	LLR -11.81	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 18 kb · p 0.45 · regional, not allelic
Overall
CADD	23.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0197% Admixed American · 9/45,748 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00766%

Overall 0.000909% 11/1,210,120 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0197%	5,083
Remaining individualsnot grpmax-eligible	0.0021%	47,614
European (non-Finnish)	0.000112%	895,375

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.Asn445Ser
Coding: c.1334A>G
MANE Select: NM_001113490
dbSNP: rs964738689
Type: single nucleotide variant
Location: chrX:112815416 (GRCh38)
Structure: AlphaFold pLDDT 58.16 · 18 PDB
Residue 445: the 'involved in interaction with yap1' region

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-asn445ser (accessed [today's date]).

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