Is ASTN1 p.Pro672Leu (c.2015C>T) pathogenic?

ASTN1 p.Pro672Leu (c.2015C>T) is classified Uncertain significance in ASTN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). Very rare (popmax 8.47e-05%, nfe).

How common is ASTN1 p.Pro672Leu (c.2015C>T) in the general population?

ASTN1 p.Pro672Leu (c.2015C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

ASTN1 p.Pro672Leu

c.2015C>T · VCV3319157

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.147	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 85 kb · p 0.052 · regional, not allelic
Overall
CADD	21.0	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 6.84e-05% 1/1,461,734 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: ASTN1
Protein: p.Pro672Leu
Coding: c.2015C>T
MANE Select: NM_004319
Type: single nucleotide variant
Location: chr1:176949224 (GRCh38)
Gene constraint: LOEUF 0.392 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 64.88
Residue 672: a disulfide bond; the egf-like 3 domain

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-pro672leu (accessed [today's date]).

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