Is ATN1 p.Pro326Ser (c.976C>T) pathogenic?

ATN1 p.Pro326Ser (c.976C>T) is classified Uncertain significance in ATN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-30). AlphaMissense: likely benign (0.0812); Very rare (popmax 0.000595%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ATN1 p.Pro326Ser (c.976C>T)?

ATN1 p.Pro326Ser (c.976C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ATN1 p.Pro326Ser (c.976C>T) in the general population?

ATN1 p.Pro326Ser (c.976C>T) is very rare (popmax 0.000595%, nfe) (gnomAD).

What do computational predictors say about ATN1 p.Pro326Ser (c.976C>T)?

AlphaMissense predicts likely benign (score 0.0812) — an in-silico prediction, not a clinical call.

ATN1 p.Pro326Ser

c.976C>T · VCV4171145

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0812 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000595%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0812	likely benign
REVEL	0.016	strongly benign-leaning
SaProt	LLR -7.33	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 3.3	GERP 1.5, phastCons 0.99
Regional constraint	o/e 1.08	unconstrained · MANE · 2,792 bp · p 0.013 · regional, not allelic
Overall
CADD	16.09	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 0.000595% European (non-Finnish) · 7/1,176,346 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000481% 7/1,455,946 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.Pro326Ser
Coding: c.976C>T
MANE Select: NM_001940
Type: single nucleotide variant
Location: chr12:6936243 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.25
Residue 326: 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-pro326ser (accessed [today's date]).

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