Is AMOT p.Ser962Ala (c.2884T>G) pathogenic?

AMOT p.Ser962Ala (c.2884T>G) is classified Likely benign in AMOT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-13). AlphaMissense: likely benign (0.044); Ultra-rare (popmax 0.0153%, amr).

How common is AMOT p.Ser962Ala (c.2884T>G) in the general population?

AMOT p.Ser962Ala (c.2884T>G) is ultra-rare (popmax 0.0153%, amr) (gnomAD).

What do computational predictors say about AMOT p.Ser962Ala (c.2884T>G)?

AlphaMissense predicts likely benign (score 0.044) — an in-silico prediction, not a clinical call.

AMOT p.Ser962Ala

c.2884T>G · rs200613321 · VCV2252666

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.044 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0153%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.044	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -3.57	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.1	GERP -3.3, phastCons 0.009
Regional constraint	o/e 0.89	unconstrained · MANE · 12 kb · p 0.066 · regional, not allelic
Overall
CADD	1.636	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 0.0153% Admixed American · 6/39,191 alleles

Filtering AF 0.00941% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00843%

Overall 0.00894% 57/637,562 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0153%	6,532
Remaining individualsnot grpmax-eligible	0.0141%	7,106
European (non-Finnish)	0.0122%	8,179

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.Ser962Ala
Coding: c.2884T>G
MANE Select: NM_001113490
dbSNP: rs200613321
Type: single nucleotide variant
Location: chrX:112779270 (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.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-ser962ala (accessed [today's date]).

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