Is ASPNAT p.Pro52Ser (c.154C>T) pathogenic?

ASPNAT p.Pro52Ser (c.154C>T) is classified Uncertain significance in ASPNAT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-17). AlphaMissense: likely benign (0.087); Very rare (popmax 0.000365%, nfe).

How common is ASPNAT p.Pro52Ser (c.154C>T) in the general population?

ASPNAT p.Pro52Ser (c.154C>T) is very rare (popmax 0.000365%, nfe) (gnomAD).

What do computational predictors say about ASPNAT p.Pro52Ser (c.154C>T)?

AlphaMissense predicts likely benign (score 0.087) — an in-silico prediction, not a clinical call.

ASPNAT p.Pro52Ser

c.154C>T · rs1394330348 · VCV3176583

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.087 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000365%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.087	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -8.08	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 0.26	GERP 0.57, phastCons 0.12
Regional constraint	o/e 1.01	unconstrained · MANE · 1,534 bp · p 0.84 · regional, not allelic
Overall
CADD	14.56	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

Grpmax group 0.000365% European (non-Finnish) · 3/822,320 alleles

Filtering AF 9.7e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.7e-05%

Overall 0.000307% 3/976,218 alleles · very rare exomes 3/830,342 · genomes 0/145,876 · joint denominator

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.Pro52Ser
Coding: c.154C>T
MANE Select: NM_178557
dbSNP: rs1394330348
Type: single nucleotide variant
Location: chr4:2059665 (GRCh38)
Structure: AlphaFold pLDDT 81.36
Residue 52: 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-pro52ser (accessed [today's date]).

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