Is ATN1 p.Arg16Pro (c.47G>C) pathogenic?

ATN1 p.Arg16Pro (c.47G>C) is classified Uncertain significance in ATN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-26). AlphaMissense: likely pathogenic (0.9752); Very rare (popmax 8.49e-05%, nfe).

How common is ATN1 p.Arg16Pro (c.47G>C) in the general population?

ATN1 p.Arg16Pro (c.47G>C) is very rare (popmax 8.49e-05%, nfe) (gnomAD).

What do computational predictors say about ATN1 p.Arg16Pro (c.47G>C)?

AlphaMissense predicts likely pathogenic (score 0.9752) — an in-silico prediction, not a clinical call.

ATN1 p.Arg16Pro

c.47G>C · VCV4078045

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9752 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.49e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9752	likely pathogenic
REVEL	0.491	indeterminate
SaProt	LLR -7.16	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 1,630 bp · p 0.025 · regional, not allelic
Overall
CADD	32.0	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 8.49e-05% European (non-Finnish) · 1/1,177,924 alleles

Overall 0.000657% 1/152,200 alleles · very 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: ATN1
Protein: p.Arg16Pro
Coding: c.47G>C
MANE Select: NM_001940
Type: single nucleotide variant
Location: chr12:6934195 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.25
Residue 16: the 'disordered' region

Full ATN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ATN1 p.His1052Pro Pathogenic/Likely pathogenic ★★ same type
ATN1 p.Ser1059Leu Pathogenic/Likely pathogenic ★★ same type
ATN1 p.Arg1152Cys Uncertain significance ★★ ⚠ same type
ATN1 p.Asn422Ser Uncertain significance ★★ ⚠ same type
ATN1 p.Glu814Gly Uncertain significance ★★ ⚠ same type
ATN1 p.Met335Ile Uncertain significance ★★ ⚠ same type
ATN1 p.Pro185Ala Uncertain significance ★★ ⚠ same type
ATN1 p.Pro720Ser 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/atn1-p-arg16pro (accessed [today's date]).

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