Is ASPNAT p.Pro115= (c.345G>A) pathogenic?

ASPNAT p.Pro115= (c.345G>A) is classified Likely benign in ASPNAT (ClinVar, Single submitter, 1 submitter; last evaluated 2017-06-22). Very rare (popmax 9.49e-05%, nfe).

How common is ASPNAT p.Pro115= (c.345G>A) in the general population?

ASPNAT p.Pro115= (c.345G>A) is very rare (popmax 9.49e-05%, nfe) (gnomAD).

ASPNAT p.Pro115=

c.345G>A · rs1577665579 · VCV782991

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 9.49e-05%, 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 3.3	GERP 0.13, phastCons 1
Overall
CADD	15.27	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 9.49e-05% European (non-Finnish) · 1/1,053,382 alleles

Overall 8.16e-05% 1/1,225,860 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: ASPNAT
Protein: p.Pro115=
Coding: c.345G>A
MANE Select: NM_178557
dbSNP: rs1577665579
Type: single nucleotide variant
Location: chr4:2059856 (GRCh38)
Structure: AlphaFold pLDDT 81.36

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

Similar variants

ASPNAT p.Pro115Arg Uncertain significance ★ ⚠ same residue
ASPNAT p.Pro115Leu Uncertain significance ★ ⚠ same residue
ASPNAT c.541+8C>T Benign ★★ same type
ASPNAT p.Ala35= Likely benign ★★ same type
ASPNAT p.Gly263= Likely benign ★★ same type
ASPNAT p.Pro56= Likely benign ★★ same type
ASPNAT p.Ala125Thr Uncertain significance ★ ⚠ same type
ASPNAT p.Ala225Thr 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/aspnat-p-pro115 (accessed [today's date]).

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