Is ATN1 p.Pro464= (c.1392C>T) pathogenic?

ATN1 p.Pro464= (c.1392C>T) is classified Likely benign in ATN1 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-05-01). Ultra-rare (popmax 0.036%, nfe).

How common is ATN1 p.Pro464= (c.1392C>T) in the general population?

ATN1 p.Pro464= (c.1392C>T) is ultra-rare (popmax 0.036%, nfe) (gnomAD).

ATN1 p.Pro464=

c.1392C>T · rs143104309 · VCV2642644

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.036%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.51	GERP -2.4, phastCons 0.029
Overall
CADD	0.794	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.036% European (non-Finnish) · 425/1,179,966 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0321%

Overall 0.0276% 445/1,613,764 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.036%	2,776
Remaining individualsnot grpmax-eligible	0.0208%	4,806
African / African-American	0.00668%	14,962
South Asian	0.0022%	45,542

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.Pro464=
Coding: c.1392C>T
MANE Select: NM_001940
dbSNP: rs143104309
Type: single nucleotide variant
Location: chr12:6936659 (GRCh38)
Gene constraint: LOEUF 0.352 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 49.25
Residue 464: 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-pro464 (accessed [today's date]).

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