Is NAF1 p.Pro445= (c.1335A>G) pathogenic?

NAF1 p.Pro445= (c.1335A>G) is classified Likely benign in NAF1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-12-28). Absent from gnomAD v4.1; Associated with NAF1-related disorder.

What condition is associated with NAF1 p.Pro445= (c.1335A>G)?

NAF1 p.Pro445= (c.1335A>G) is associated with NAF1-related disorder (ClinVar).

How common is NAF1 p.Pro445= (c.1335A>G) in the general population?

NAF1 p.Pro445= (c.1335A>G) is absent from gnomAD v4.1 (gnomAD).

NAF1 p.Pro445=

c.1335A>G · rs1278724671 · VCV3029121

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

NAF1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.98	GERP -2.9, phastCons 0.006
Overall
CADD	6.079	PHRED · no single calibrated threshold — expert panels disagree

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: NAF1
Protein: p.Pro445=
Coding: c.1335A>G
MANE Select: NM_138386
dbSNP: rs1278724671
Type: single nucleotide variant
Location: chr4:163129047 (GRCh38)
Structure: AlphaFold pLDDT 72.47 · 8 PDB
Residue 445: the 'required for inhibitory activity of tnf-induced nf-kappa-b activation' region

Full NAF1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

NAF1-related disorder

Similar variants

NAF1 p.Pro445Gln Uncertain significance ★★ ⚠ same residue
NAF1 p.Pro445Arg Uncertain significance ★ ⚠ same residue
NAF1 p.Ile190Val Uncertain significance ★★ ⚠ same condition
NAF1 p.Asn17Tyr Uncertain significance ★ ⚠ same condition
NAF1 p.Pro359Leu Uncertain significance ★ same condition
NAF1 p.Ala87= Likely benign same condition
NAF1 p.Pro250= Likely benign same condition
NAF1 p.Thr97= Likely benign same condition

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/naf1-p-pro445 (accessed [today's date]).

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