NDUFAF2 p.Phe154=
c.462T>C · rs77878573 · VCV138457
Benign/Likely benign
Multiple submitters
Classification
Benign/Likely benign
ClinVar
Review
Multiple submitters ★★☆☆
ClinVar · 6 submitters
gnomAD v4.1
Common
common (popmax 6.16%, afr) — too common for a highly-penetrant pathogenic allele
Conditions
3
mitochondrial complex I deficiency, nuclear type 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 -0.53 | GERP -3.9, phastCons 0.094 |
| Overall | ||
| CADD | 4.576 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
6.16%
African / African-American · 4,618/75,022 alleles
Filtering AF
6.01%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 5.95%
Overall
0.311%
5,017/1,613,530 alleles · common
exomes 2,445/1,461,232 · genomes 2,572/152,298 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| African / African-Americangrpmax | 6.16% | 16 |
| Remaining individualsnot grpmax-eligible | 0.328% | 305 |
| Admixed American | 0.243% | 411 |
| Middle Eastern | 0.0495% | 2,021 |
| South Asian | 0.0121% | 8,271 |
| European (non-Finnish) | 0.0028% | 35,749 |
| East Asian | 0.00223% | 44,836 |
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
- NDUFAF2
- Protein
- p.Phe154=
- Coding
- c.462T>C
- MANE Select
- NM_174889
- dbSNP
- rs77878573
- Type
- single nucleotide variant
- Location
- chr5:61152907 (GRCh38)
- Gene constraint
- LOEUF 1.107 · pLI 0.02 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
- Structure
- AlphaFold pLDDT 78.98
- Residue 154
- the 'disordered' region; a UniProt-annotated variant site (in mc1dn10); a UniProt-annotated variant site (in mc1dn10; patient cells homozygous for the variant do not express detectable amounts of protein; complex i assembly is altered and activity is severely reduced in patient cells compared to control)
Similar variants
- NDUFAF2 p.Arg47Ter Pathogenic/Likely pathogenic ★★ same condition
- NDUFAF2 p.Met1Leu Pathogenic/Likely pathogenic ★★ same condition
- NDUFAF2 p.Trp74Ter Pathogenic/Likely pathogenic ★★ same condition
- NDUFAF2 p.Ile88Thr Uncertain significance ★★ ⚠ same condition
- NDUFAF2 p.Tyr34His Uncertain significance ★★ ⚠ same condition
- NDUFAF2 c.217+42A>G Benign ★★ same condition
- NDUFAF2 p.Ile100= Benign/Likely benign ★★ same condition
- NDUFAF2 p.Lys20= 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/ndufaf2-p-phe154 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown