Is AMOT p.Gln642His (c.1926G>C) pathogenic?

AMOT p.Gln642His (c.1926G>C) is classified Likely pathogenic in AMOT (ClinVar, Single submitter, 1 submitter; last evaluated 2015-09-09). AlphaMissense: likely pathogenic (0.8364); Absent from gnomAD v4.1; Associated with Cerebral visual impairment and intellectual disability.

What condition is associated with AMOT p.Gln642His (c.1926G>C)?

AMOT p.Gln642His (c.1926G>C) is associated with Cerebral visual impairment and intellectual disability (ClinVar).

How common is AMOT p.Gln642His (c.1926G>C) in the general population?

AMOT p.Gln642His (c.1926G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMOT p.Gln642His (c.1926G>C)?

AlphaMissense predicts likely pathogenic (score 0.8364) — an in-silico prediction, not a clinical call.

AMOT p.Gln642His

c.1926G>C · rs869312862 · VCV224811

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8364 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Cerebral visual impairment and intellectual disability

Computational evidence

Protein change
AlphaMissense	0.8364	likely pathogenic ✓ concordant with ClinVar
REVEL	0.265	benign-leaning
SaProt	LLR -8.17	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	Δ0.98	donor loss · deltas
Pangolin	Δ0.86	loss · gain 0.72 · agrees with SpliceAI · independent
Constraint at this position
Conservation	phyloP 6	GERP 1.1, phastCons 1
Regional constraint	o/e 0.58	unconstrained · MANE · 14 kb · p 1e-05 · regional, not allelic
Overall
CADD	35.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: AMOT
Protein: p.Gln642His
Coding: c.1926G>C
MANE Select: NM_001113490
dbSNP: rs869312862
Type: single nucleotide variant
Location: chrX:112791832 (GRCh38)
Structure: AlphaFold pLDDT 58.16 · 18 PDB
Residue 642: the 'involved in interaction with yap1' region

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

Disease context

Cerebral visual impairment and intellectual disability

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.Ala1023Pro Uncertain significance ★ ⚠ same type
AMOT p.Ala460Gly Uncertain significance ★ ⚠ same type
AMOT p.Ala703Thr 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-gln642his (accessed [today's date]).

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