Is AMOT p.Ser538= (c.1614G>A) pathogenic?

AMOT p.Ser538= (c.1614G>A) is classified Benign in AMOT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). Common (popmax 5.73%, afr) — too common for a highly-penetrant pathogenic allele.

AMOT p.Ser538=

Q: How common is AMOT p.Ser538= (c.1614G>A) in the general population?

AMOT p.Ser538= (c.1614G>A) is common (popmax 5.73%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1614G>A · rs57201849 · VCV782827

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 5.73%, afr) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP -3.4, phastCons 1
Overall
CADD	2.747	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 5.73% African / African-American · 3,275/57,200 alleles

Filtering AF 5.56% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.5%

Overall 0.349% 4,215/1,209,437 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	5.73%	17
Admixed American	0.685%	146
Remaining individualsnot grpmax-eligible	0.489%	204
Middle Eastern	0.323%	310
Ashkenazi Jewishnot grpmax-eligible	0.177%	565
European (non-Finnish)	0.0361%	2,770
South Asian	0.0176%	5,677
Finnishnot grpmax-eligible	0.0151%	6,627

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.Ser538=
Coding: c.1614G>A
MANE Select: NM_001113490
dbSNP: rs57201849
Type: single nucleotide variant
Location: chrX:112809910 (GRCh38)
Structure: AlphaFold pLDDT 58.16 · 18 PDB
Residue 538: 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.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
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-ser538 (accessed [today's date]).

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