Is AMOT p.Val600Ile (c.1798G>A) pathogenic?

AMOT p.Val600Ile (c.1798G>A) is classified Uncertain significance in AMOT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-02). AlphaMissense: likely pathogenic (0.5693); Very rare (popmax 0.00876%, afr).

How common is AMOT p.Val600Ile (c.1798G>A) in the general population?

AMOT p.Val600Ile (c.1798G>A) is very rare (popmax 0.00876%, afr) (gnomAD).

What do computational predictors say about AMOT p.Val600Ile (c.1798G>A)?

AlphaMissense predicts likely pathogenic (score 0.5693) — an in-silico prediction, not a clinical call.

AMOT p.Val600Ile

c.1798G>A · VCV4640254

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5693 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00876%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5693	likely pathogenic
REVEL	0.215	benign-leaning
SaProt	LLR -8.20	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 14 kb · p 1e-05 · regional, not allelic
Overall
CADD	23.7	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 0.00876% African / African-American · 5/57,106 alleles

Filtering AF 0.00339% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00215%

Overall 0.0019% 23/1,209,207 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00876%	11,421
Finnishnot grpmax-eligible	0.00429%	23,294
Admixed American	0.00219%	45,606
European (non-Finnish)	0.00168%	59,659

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.Val600Ile
Coding: c.1798G>A
MANE Select: NM_001113490
Type: single nucleotide variant
Location: chrX:112791960 (GRCh38)
Structure: AlphaFold pLDDT 58.16 · 18 PDB
Residue 600: 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-val600ile (accessed [today's date]).

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