Is NFU1 p.Pro69= (c.207A>G) pathogenic?

NFU1 p.Pro69= (c.207A>G) is classified Likely benign in NFU1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-09). Absent from gnomAD v4.1; Associated with multiple mitochondrial dysfunctions syndrome 1.

What condition is associated with NFU1 p.Pro69= (c.207A>G)?

NFU1 p.Pro69= (c.207A>G) is associated with multiple mitochondrial dysfunctions syndrome 1 (ClinVar).

How common is NFU1 p.Pro69= (c.207A>G) in the general population?

NFU1 p.Pro69= (c.207A>G) is absent from gnomAD v4.1 (gnomAD).

NFU1 p.Pro69=

Q: How is Multiple mitochondrial dysfunctions syndrome type 1 inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.207A>G · rs2466398835 · VCV2854424

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

multiple mitochondrial dysfunctions syndrome 1

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 -0.19, phastCons 1
Overall
CADD	12.11	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: NFU1
Protein: p.Pro69=
Coding: c.207A>G
MANE Select: NM_001002755
dbSNP: rs2466398835
Type: single nucleotide variant
Location: chr2:69423677 (GRCh38)
Gene constraint: LOEUF 1.544 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.07 · 2 PDB

Full NFU1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

multiple mitochondrial dysfunctions syndrome 1 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Multiple mitochondrial dysfunctions syndrome type 1 (Orphanet):

Inheritance: Autosomal recessive
Onset: Neonatal

Similar variants

NFU1 p.Pro69Arg Uncertain significance ★ ⚠ same residue
NFU1 c.303-2A>T Likely pathogenic ★★ same condition
NFU1 c.545+5G>A Pathogenic ★★ same condition
NFU1 c.62+89G>A Pathogenic/Likely pathogenic ★★ same condition
NFU1 p.Arg182Gln Pathogenic/Likely pathogenic ★★ same condition
NFU1 p.Arg182Trp Pathogenic ★★ same condition
NFU1 p.Gly208Cys Pathogenic ★★ same condition
NFU1 p.Ala100Gly Uncertain significance ★★ ⚠ 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/nfu1-p-pro69 (accessed [today's date]).

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