Is AMOT p.Ser316Phe (c.947C>T) pathogenic?

AMOT p.Ser316Phe (c.947C>T) is classified Uncertain significance in AMOT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-27). AlphaMissense: likely benign (0.3181); Absent from gnomAD v4.1.

How common is AMOT p.Ser316Phe (c.947C>T) in the general population?

AMOT p.Ser316Phe (c.947C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about AMOT p.Ser316Phe (c.947C>T)?

AlphaMissense predicts likely benign (score 0.3181) — an in-silico prediction, not a clinical call.

AMOT p.Ser316Phe

c.947C>T · rs2521666535 · VCV2313865

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3181 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3181	likely benign
REVEL	0.177	moderately benign-leaning
SaProt	LLR -10.28	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 18 kb · p 0.45 · regional, not allelic
Overall
CADD	23.6	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.Ser316Phe
Coding: c.947C>T
MANE Select: NM_001113490
dbSNP: rs2521666535
Type: single nucleotide variant
Location: chrX:112815803 (GRCh38)
Structure: AlphaFold pLDDT 58.16 · 18 PDB
Residue 316: the 'disordered' region

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

Similar variants

AMOT p.Ser316= Benign ★★ same residue
AMOT p.Ala1032Val 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-ser316phe (accessed [today's date]).

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