Is AMER1 p.Ser17Cys (c.50C>G) pathogenic?

AMER1 p.Ser17Cys (c.50C>G) is classified Uncertain significance in AMER1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-14). AlphaMissense: likely benign (0.1115); Ultra-rare (popmax 0.0246%, sas); Associated with osteopathia striata with cranial sclerosis.

What condition is associated with AMER1 p.Ser17Cys (c.50C>G)?

AMER1 p.Ser17Cys (c.50C>G) is associated with osteopathia striata with cranial sclerosis (ClinVar).

How common is AMER1 p.Ser17Cys (c.50C>G) in the general population?

AMER1 p.Ser17Cys (c.50C>G) is ultra-rare (popmax 0.0246%, sas) (gnomAD).

What do computational predictors say about AMER1 p.Ser17Cys (c.50C>G)?

AlphaMissense predicts likely benign (score 0.1115) — an in-silico prediction, not a clinical call.

AMER1 p.Ser17Cys

c.50C>G · rs528118163 · VCV2439014

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1115 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0246%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

osteopathia striata with cranial sclerosis

Computational evidence

Protein change
AlphaMissense	0.1115	likely benign
REVEL	0.014	strongly benign-leaning
SaProt	LLR -8.45	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 4.8	GERP -2, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 3,404 bp · p 0.037 · regional, not allelic
Overall
CADD	16.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0246% South Asian · 14/56,995 alleles

Filtering AF 0.0148% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0119%

Overall 0.00127% 14/1,098,237 alleles · ultra-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: AMER1
Protein: p.Ser17Cys
Coding: c.50C>G
MANE Select: NM_152424
dbSNP: rs528118163
Type: single nucleotide variant
Location: chrX:64193237 (GRCh38)
Structure: AlphaFold pLDDT 48.88 · 3 PDB
Residue 17: the 'disordered' region

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

Disease context

osteopathia striata with cranial sclerosis — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

AMER1 p.Ser17Phe Uncertain significance ★ ⚠ same residue
AMER1 p.Arg353Ter Pathogenic ★★ same condition
AMER1 p.Arg358Ter Pathogenic ★★ same condition
AMER1 p.Arg497Ter Pathogenic/Likely pathogenic ★★ same condition
AMER1 p.Gln189Ter Pathogenic ★★ same condition
AMER1 p.Gln335Ter Pathogenic ★★ same condition
AMER1 p.Arg77Trp Uncertain significance ★★ ⚠ same condition
AMER1 p.Gln213Arg Uncertain significance ★★ ⚠ same condition

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-ser17cys (accessed [today's date]).

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