Is NAF1 p.Pro69= (c.207C>G) pathogenic?

NAF1 p.Pro69= (c.207C>G) is classified Likely benign in NAF1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-18). Very rare (popmax 0.00172%, amr).

How common is NAF1 p.Pro69= (c.207C>G) in the general population?

NAF1 p.Pro69= (c.207C>G) is very rare (popmax 0.00172%, amr) (gnomAD).

NAF1 p.Pro69=

c.207C>G · VCV4968994

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00172%, amr)

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 -1.6	GERP -2.6
Overall
CADD	5.375	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00172% Admixed American · 1/58,184 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000375% 6/1,599,028 alleles · very rare exomes 6/1,446,740 · genomes 0/152,288 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00172%	58,184
Remaining individualsnot grpmax-eligible	0.00162%	61,710
South Asian	0.00112%	89,680
European (non-Finnish)	0.000256%	390,929

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.Pro69=
Coding: c.207C>G
MANE Select: NM_138386
Type: single nucleotide variant
Location: chr4:163166521 (GRCh38)
Structure: AlphaFold pLDDT 72.47 · 8 PDB
Residue 69: the 'disordered' region

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

Similar variants

TNIP1 p.Asp69Gly 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-pro69 (accessed [today's date]).

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