Is NAF1 p.Pro438= (c.1314T>G) pathogenic?

NAF1 p.Pro438= (c.1314T>G) is classified Likely benign in NAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-19). Very rare (popmax 0.000333%).

How common is NAF1 p.Pro438= (c.1314T>G) in the general population?

NAF1 p.Pro438= (c.1314T>G) is very rare (popmax 0.000333%) (gnomAD).

NAF1 p.Pro438=

c.1314T>G · rs1033213554 · VCV2784184

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000333%)

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 -0.69	GERP -2.6, phastCons 0.92
Overall
CADD	0.065	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000333%

Overall 0.000333% 2/600,724 alleles · very rare exomes 2/587,778 · genomes 0/12,946 · 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: NAF1
Protein: p.Pro438=
Coding: c.1314T>G
MANE Select: NM_138386
dbSNP: rs1033213554
Type: single nucleotide variant
Location: chr4:163129068 (GRCh38)
Structure: AlphaFold pLDDT 72.47 · 8 PDB

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

Similar variants

TNIP1 p.Thr438Ile Uncertain significance ★ ⚠ same residue
NAF1 p.Ala102Ser Uncertain significance ★★ ⚠ same type
NAF1 p.Ala323Val Uncertain significance ★★ ⚠ same type
NAF1 p.Ala87Val Uncertain significance ★★ ⚠ same type
NAF1 p.Arg106Trp Uncertain significance ★★ ⚠ same type
NAF1 p.Arg437Cys Uncertain significance ★★ ⚠ same type
NAF1 p.Arg437His Uncertain significance ★★ ⚠ same type
NAF1 p.Asn17Ser 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/naf1-p-pro438 (accessed [today's date]).

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