Is NAP1L4 p.Ser299Phe (c.896C>T) pathogenic?

NAP1L4 p.Ser299Phe (c.896C>T) is classified Uncertain significance in NAP1L4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-17). AlphaMissense: likely benign (0.1588); Absent from gnomAD v4.1.

How common is NAP1L4 p.Ser299Phe (c.896C>T) in the general population?

NAP1L4 p.Ser299Phe (c.896C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NAP1L4 p.Ser299Phe (c.896C>T)?

AlphaMissense predicts likely benign (score 0.1588) — an in-silico prediction, not a clinical call.

NAP1L4 p.Ser299Phe

c.896C>T · VCV3298429

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1588 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1588	likely benign
REVEL	0.167	moderately benign-leaning
SaProt	LLR -10.38	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 12	GERP 1.3, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 23 kb · p 0.00065 · regional, not allelic
Overall
CADD	25.1	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

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: NAP1L4
Protein: p.Ser299Phe
Coding: c.896C>T
MANE Select: NM_005969
Type: single nucleotide variant
Location: chr11:2955763 (GRCh38)
Gene constraint: LOEUF 0.385 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 81.28

Full NAP1L4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NAP1L4 p.Thr111= Benign ★★ same type
NAP1L4 p.Ala314Val Uncertain significance ★ ⚠ same type
NAP1L4 p.Ala40Gly Uncertain significance ★ ⚠ same type
NAP1L4 p.Ala97Val Uncertain significance ★ ⚠ same type
NAP1L4 p.Arg330Gln Uncertain significance ★ ⚠ same type
NAP1L4 p.Arg44Gln Uncertain significance ★ ⚠ same type
NAP1L4 p.Arg44Leu Uncertain significance ★ ⚠ same type
NAP1L4 p.Arg93Gly 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/nap1l4-p-ser299phe (accessed [today's date]).

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