Is ATN1 p.Pro286Ser (c.856C>T) pathogenic?

ATN1 p.Pro286Ser (c.856C>T) is classified Uncertain significance in ATN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-16). AlphaMissense: likely benign (0.0713); Ultra-rare (popmax 0.0545%, sas); Associated with Inborn genetic diseases.

What condition is associated with ATN1 p.Pro286Ser (c.856C>T)?

ATN1 p.Pro286Ser (c.856C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ATN1 p.Pro286Ser (c.856C>T) in the general population?

ATN1 p.Pro286Ser (c.856C>T) is ultra-rare (popmax 0.0545%, sas) (gnomAD).

What do computational predictors say about ATN1 p.Pro286Ser (c.856C>T)?

AlphaMissense predicts likely benign (score 0.0713) — an in-silico prediction, not a clinical call.

ATN1 p.Pro286Ser

c.856C>T · rs782682486 · VCV2278808

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0713 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0545%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0713	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -6.54	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 -0.073	GERP -3.1
Regional constraint	o/e 1.08	unconstrained · MANE · 2,792 bp · p 0.013 · regional, not allelic
Overall
CADD	13.92	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 0.0545% South Asian · 42/77,098 alleles

Filtering AF 0.0414% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0368%

Overall 0.00287% 44/1,530,940 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0545%	1,836
East Asian	0.00226%	44,244
Remaining individualsnot grpmax-eligible	0.0017%	58,790

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.Pro286Ser
Coding: c.856C>T
MANE Select: NM_001940
dbSNP: rs782682486
Type: single nucleotide variant
Location: chr12:6936123 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.25
Residue 286: the 'disordered' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ATN1 p.Arg1152Cys Uncertain significance ★★ ⚠ same condition
ATN1 p.Asn422Ser Uncertain significance ★★ ⚠ same condition
ATN1 p.Glu814Gly Uncertain significance ★★ ⚠ same condition
ATN1 p.Met335Ile Uncertain significance ★★ ⚠ same condition
ATN1 p.Pro185Ala Uncertain significance ★★ ⚠ same condition
ATN1 p.Pro720Ser Uncertain significance ★★ ⚠ same condition
ATN1 p.Pro970Ser Uncertain significance ★★ ⚠ same condition
ATN1 p.Ser379Ile 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/atn1-p-pro286ser (accessed [today's date]).

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