Is NAPRT p.Ala306Ser (c.916G>T) pathogenic?

NAPRT p.Ala306Ser (c.916G>T) is classified Uncertain significance in NAPRT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely benign (0.1375); Ultra-rare (popmax 0.0156%, eas).

How common is NAPRT p.Ala306Ser (c.916G>T) in the general population?

NAPRT p.Ala306Ser (c.916G>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about NAPRT p.Ala306Ser (c.916G>T)?

AlphaMissense predicts likely benign (score 0.1375) — an in-silico prediction, not a clinical call.

NAPRT p.Ala306Ser

c.916G>T · VCV3917237

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1375 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1375	likely benign
REVEL	0.27	benign-leaning
SaProt	LLR -10.15	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.1, phastCons 1
Regional constraint	o/e 1.12	unconstrained · MANE · 3,477 bp · p 0.0014 · regional, not allelic
Overall
CADD	24.5	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 0.0156% East Asian · 7/44,844 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000496% 8/1,611,996 alleles · ultra-rare exomes 7/1,459,974 · genomes 1/152,022 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,406
South Asian	0.0011%	90,996

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.Ala306Ser
Coding: c.916G>T
MANE Select: NM_145201
Type: single nucleotide variant
Location: chr8:143576538 (GRCh38)
Gene constraint: LOEUF 1.486 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.94 · 1 PDB
Residue 306: an α-helix

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-ala306ser (accessed [today's date]).

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