Is AMER1 p.Pro160Ser (c.478C>T) pathogenic?

AMER1 p.Pro160Ser (c.478C>T) is classified Benign/Likely benign in AMER1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-07). AlphaMissense: likely benign (0.0762); Rare (popmax 0.166%, sas).

How common is AMER1 p.Pro160Ser (c.478C>T) in the general population?

AMER1 p.Pro160Ser (c.478C>T) is rare (popmax 0.166%, sas) (gnomAD).

What do computational predictors say about AMER1 p.Pro160Ser (c.478C>T)?

AlphaMissense predicts likely benign (score 0.0762) — an in-silico prediction, not a clinical call.

AMER1 p.Pro160Ser

c.478C>T · rs760337524 · VCV2901797

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0762 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.166%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0762	likely benign
REVEL	0.019	moderately benign-leaning
SaProt	LLR -5.85	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 1.8	GERP -3.1, phastCons 0.1
Regional constraint	o/e 1.07	unconstrained · MANE · 3,404 bp · p 0.037 · regional, not allelic
Overall
CADD	0.49	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 0.166% South Asian · 94/56,795 alleles

Filtering AF 0.138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.128%

Overall 0.00835% 101/1,210,104 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.166%	604
Remaining individualsnot grpmax-eligible	0.0105%	9,518
European (non-Finnish)	0.000223%	447,646

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: AMER1
Protein: p.Pro160Ser
Coding: c.478C>T
MANE Select: NM_152424
dbSNP: rs760337524
Type: single nucleotide variant
Location: chrX:64192809 (GRCh38)
Structure: AlphaFold pLDDT 48.88 · 3 PDB
Residue 160: the 'disordered' region

Full AMER1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

AMER1 p.Arg353Ter Pathogenic ★★ same type
AMER1 p.Arg358Ter Pathogenic ★★ same type
AMER1 p.Arg497Ter Pathogenic/Likely pathogenic ★★ same type
AMER1 p.Gln189Ter Pathogenic ★★ same type
AMER1 p.Gln335Ter Pathogenic ★★ same type
AMER1 p.Glu191Ter Pathogenic/Likely pathogenic ★★ same type
AMER1 p.Ala202Gly Uncertain significance ★★ ⚠ same type
AMER1 p.Ala229Pro 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/amer1-p-pro160ser (accessed [today's date]).

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