Is ASTN1 p.Pro443= (c.1329T>C) pathogenic?

ASTN1 p.Pro443= (c.1329T>C) is classified Likely benign in ASTN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-01). Absent from gnomAD v4.1.

How common is ASTN1 p.Pro443= (c.1329T>C) in the general population?

ASTN1 p.Pro443= (c.1329T>C) is absent from gnomAD v4.1 (gnomAD).

ASTN1 p.Pro443=

c.1329T>C · rs2525289417 · VCV3026650

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 0.3	GERP -3.8, phastCons 0.59
Overall
CADD	8.464	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ASTN1
Protein: p.Pro443=
Coding: c.1329T>C
MANE Select: NM_004319
dbSNP: rs2525289417
Type: single nucleotide variant
Location: chr1:177023513 (GRCh38)
Gene constraint: LOEUF 0.392 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.88

Full ASTN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ASTN1 p.Asp1150Tyr Uncertain significance ★★ same type
ASTN1 p.His419Asn Uncertain significance ★★ same type
ASTN1 p.Ser290Gly Uncertain significance ★★ same type
ASTN1 p.Val1025Leu Uncertain significance ★★ same type
ASTN1 p.Arg1112Ter Likely pathogenic ★ same type
ASTN1 p.Gly742Arg Likely pathogenic ★ same type
ASTN1 c.1523+1G>T Uncertain significance ★ same type
ASTN1 p.Ala2Thr 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/astn1-p-pro443 (accessed [today's date]).

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