Is ASTN1 p.Pro16Ala (c.46C>G) pathogenic?

ASTN1 p.Pro16Ala (c.46C>G) is classified Uncertain significance in ASTN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-30). Very rare (popmax 0.00134%, afr).

How common is ASTN1 p.Pro16Ala (c.46C>G) in the general population?

ASTN1 p.Pro16Ala (c.46C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

ASTN1 p.Pro16Ala

c.46C>G · rs1310821264 · VCV2262901

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.128	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.85	unconstrained · MANE · 215 kb · p 7.5e-06 · regional, not allelic
Overall
CADD	20.8	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,842 alleles

Overall 6.87e-05% 1/1,454,932 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.Pro16Ala
Coding: c.46C>G
MANE Select: NM_004319
dbSNP: rs1310821264
Type: single nucleotide variant
Location: chr1:177164631 (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-pro16ala (accessed [today's date]).

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