Is NDUFB9 p.Pro8= (c.24C>T) pathogenic?

NDUFB9 p.Pro8= (c.24C>T) is classified Benign/Likely benign in NDUFB9 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-03-01). Rare (popmax 0.368%, amr); Associated with mitochondrial complex I deficiency, nuclear type 24.

What condition is associated with NDUFB9 p.Pro8= (c.24C>T)?

NDUFB9 p.Pro8= (c.24C>T) is associated with mitochondrial complex I deficiency, nuclear type 24 (ClinVar).

How common is NDUFB9 p.Pro8= (c.24C>T) in the general population?

NDUFB9 p.Pro8= (c.24C>T) is rare (popmax 0.368%, amr) (gnomAD).

NDUFB9 p.Pro8=

c.24C>T · rs147044660 · VCV138472

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.368%, amr)

Conditions

mitochondrial complex I deficiency, nuclear type 24

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 -3.2	GERP -2.2
Overall
CADD	8.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.368% Admixed American · 221/60,032 alleles

Filtering AF 0.328% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.313%

Overall 0.254% 4,099/1,614,228 alleles · rare exomes 3,722/1,461,868 · genomes 377/152,360 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.368%	272
European (non-Finnish)	0.286%	349
Ashkenazi Jewishnot grpmax-eligible	0.284%	352
Remaining individualsnot grpmax-eligible	0.283%	353
African / African-American	0.282%	354
Finnishnot grpmax-eligible	0.039%	2,561
Middle Eastern	0.0165%	6,062

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: NDUFB9
Protein: p.Pro8=
Coding: c.24C>T
MANE Select: NM_005005
dbSNP: rs147044660
Type: single nucleotide variant
Location: chr8:124539210 (GRCh38)
Gene constraint: LOEUF 1.162 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 96.04 · 7 PDB

Full NDUFB9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial complex I deficiency, nuclear type 24 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NDUFB9 p.Pro8Leu Likely benign ★★ same residue
NDUFB9 c.294+5G>T Uncertain significance ★★ same condition
NDUFB9 c.-51A>G Likely benign ★★ same condition
NDUFB9 p.Glu160Gly Uncertain significance ★ ⚠ same condition
NDUFB9 p.Thr144Met Uncertain significance ★ ⚠ same condition
NDUFB9 p.Leu64Pro Pathogenic same condition
NDUFB9 p.Arg129Gln Uncertain significance ★★ ⚠ same type
NDUFB9 p.Arg135Gln 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/ndufb9-p-pro8 (accessed [today's date]).

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