Is NAPRT p.Pro127Ser (c.379C>T) pathogenic?

NAPRT p.Pro127Ser (c.379C>T) is classified Uncertain significance in NAPRT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-22). AlphaMissense: ambiguous (0.3562); Very rare (popmax 8.7e-05%, nfe).

How common is NAPRT p.Pro127Ser (c.379C>T) in the general population?

NAPRT p.Pro127Ser (c.379C>T) is very rare (popmax 8.7e-05%, nfe) (gnomAD).

What do computational predictors say about NAPRT p.Pro127Ser (c.379C>T)?

AlphaMissense predicts ambiguous (score 0.3562) — an in-silico prediction, not a clinical call.

NAPRT p.Pro127Ser

c.379C>T · rs751144884 · VCV2605261

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3562 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.7e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3562	ambiguous
REVEL	0.3	indeterminate
SaProt	LLR -10.42	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.4, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 3,477 bp · p 0.0014 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.7e-05% European (non-Finnish) · 1/1,148,886 alleles

Overall 6.47e-05% 1/1,546,458 alleles · very rare exomes 1/1,394,116 · genomes 0/152,342 · 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: NAPRT
Protein: p.Pro127Ser
Coding: c.379C>T
MANE Select: NM_145201
dbSNP: rs751144884
Type: single nucleotide variant
Location: chr8:143577715 (GRCh38)
Gene constraint: LOEUF 1.486 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.94 · 1 PDB
Residue 127: a β-strand

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

Similar variants

NAPRT c.1447-7C>G Benign ★★ same type
NAPRT p.Asp320= Benign ★★ same type
NAPRT p.Pro117= Benign/Likely benign ★★ same type
NAPRT p.Ala13Gly Uncertain significance ★ ⚠ same type
NAPRT p.Ala159Thr Uncertain significance ★ ⚠ same type
NAPRT p.Ala231Val Uncertain significance ★ ⚠ same type
NAPRT p.Ala234Pro Uncertain significance ★ ⚠ same type
NAPRT p.Ala23Thr 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/naprt-p-pro127ser (accessed [today's date]).

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