Is ATN1 p.Pro970Ser (c.2908C>T) pathogenic?

ATN1 p.Pro970Ser (c.2908C>T) is classified Uncertain significance in ATN1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-07). AlphaMissense: likely benign (0.1439); Very rare (popmax 0.00133%, afr); Associated with Inborn genetic diseases.

What condition is associated with ATN1 p.Pro970Ser (c.2908C>T)?

ATN1 p.Pro970Ser (c.2908C>T) is associated with Inborn genetic diseases (ClinVar).

How common is ATN1 p.Pro970Ser (c.2908C>T) in the general population?

ATN1 p.Pro970Ser (c.2908C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about ATN1 p.Pro970Ser (c.2908C>T)?

AlphaMissense predicts likely benign (score 0.1439) — an in-silico prediction, not a clinical call.

ATN1 p.Pro970Ser

c.2908C>T · VCV4171042

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1439 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1439	likely benign
REVEL	0.128	moderately benign-leaning
SaProt	LLR -8.36	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 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 578 bp · p 0.00064 · regional, not allelic
Overall
CADD	26.0	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 0.00133% African / African-American · 1/75,048 alleles

Overall 6.84e-05% 1/1,461,818 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.Pro970Ser
Coding: c.2908C>T
MANE Select: NM_001940
Type: single nucleotide variant
Location: chr12:6938871 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.25

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.Ser379Ile Uncertain significance ★★ ⚠ same condition
ATN1 p.Val911Met 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-pro970ser (accessed [today's date]).

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