Is AMOT p.Pro240Gln (c.719C>A) pathogenic?

AMOT p.Pro240Gln (c.719C>A) is classified Uncertain significance in AMOT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely pathogenic (0.9606); Very rare (popmax 0.00179%, afr).

How common is AMOT p.Pro240Gln (c.719C>A) in the general population?

AMOT p.Pro240Gln (c.719C>A) is very rare (popmax 0.00179%, afr) (gnomAD).

What do computational predictors say about AMOT p.Pro240Gln (c.719C>A)?

AlphaMissense predicts likely pathogenic (score 0.9606) — an in-silico prediction, not a clinical call.

AMOT p.Pro240Gln

c.719C>A · rs1934740700 · VCV3116207

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9606 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00179%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9606	likely pathogenic
REVEL	0.435	indeterminate
SaProt	LLR -7.18	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 18 kb · p 0.45 · regional, not allelic
Overall
CADD	25.7	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 0.00179% African / African-American · 1/55,744 alleles

Overall 0.000893% 1/111,997 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.Pro240Gln
Coding: c.719C>A
MANE Select: NM_001113490
dbSNP: rs1934740700
Type: single nucleotide variant
Location: chrX:112822408 (GRCh38)
Structure: AlphaFold pLDDT 58.16 · 18 PDB
Residue 240: an α-helix; the 'disordered' 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-pro240gln (accessed [today's date]).

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