Is NAF1 p.Pro250= (c.750A>G) pathogenic?

NAF1 p.Pro250= (c.750A>G) is classified Likely benign in NAF1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-04-14). Very rare (popmax 0.00535%, afr); Associated with NAF1-related disorder.

What condition is associated with NAF1 p.Pro250= (c.750A>G)?

NAF1 p.Pro250= (c.750A>G) is associated with NAF1-related disorder (ClinVar).

How common is NAF1 p.Pro250= (c.750A>G) in the general population?

NAF1 p.Pro250= (c.750A>G) is very rare (popmax 0.00535%, afr) (gnomAD).

NAF1 p.Pro250=

c.750A>G · rs561225500 · VCV3053919

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00535%, afr)

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 -2.7	GERP -3
Overall
CADD	5.696	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00535% African / African-American · 4/74,702 alleles

Filtering AF 0.00175% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000373% 6/1,607,522 alleles · very rare exomes 2/1,455,248 · genomes 4/152,274 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00535%	18,675
Remaining individualsnot grpmax-eligible	0.00161%	62,252
South Asian	0.00112%	89,456

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.Pro250=
Coding: c.750A>G
MANE Select: NM_138386
dbSNP: rs561225500
Type: single nucleotide variant
Location: chr4:163140351 (GRCh38)
Structure: AlphaFold pLDDT 72.47 · 8 PDB
Residue 250: the 'interaction with nef' region

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

Disease context

NAF1-related disorder

Similar variants

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.Pro445= Likely benign same condition
NAF1 p.Thr97= Likely benign same condition
NAF1 p.Ala102Ser Uncertain significance ★★ ⚠ same type
NAF1 p.Ala323Val 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-pro250 (accessed [today's date]).

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