Is ASPNAT p.Pro53Ala (c.157C>G) pathogenic?

ASPNAT p.Pro53Ala (c.157C>G) is classified Uncertain significance in ASPNAT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-07). AlphaMissense: likely benign (0.0497); Absent from gnomAD v4.1.

How common is ASPNAT p.Pro53Ala (c.157C>G) in the general population?

ASPNAT p.Pro53Ala (c.157C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ASPNAT p.Pro53Ala (c.157C>G)?

AlphaMissense predicts likely benign (score 0.0497) — an in-silico prediction, not a clinical call.

ASPNAT p.Pro53Ala

c.157C>G · rs2474935240 · VCV2569409

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0497 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0497	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -6.27	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.005	GERP -0.82, phastCons 0.34
Regional constraint	o/e 1.01	unconstrained · MANE · 1,534 bp · p 0.84 · regional, not allelic
Overall
CADD	7.037	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

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: ASPNAT
Protein: p.Pro53Ala
Coding: c.157C>G
MANE Select: NM_178557
dbSNP: rs2474935240
Type: single nucleotide variant
Location: chr4:2059668 (GRCh38)
Structure: AlphaFold pLDDT 81.36
Residue 53: the 'disordered' region

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

Similar variants

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
ASPNAT p.Ala22Val Uncertain significance ★ ⚠ same type
ASPNAT p.Ala255Thr 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-pro53ala (accessed [today's date]).

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