Is UQCC2 p.Pro75= (c.225C>A) pathogenic?

UQCC2 p.Pro75= (c.225C>A) is classified Benign/Likely benign in UQCC2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-12-10). Rare (popmax 0.537%, afr); Associated with mitochondrial complex III deficiency nuclear type 7.

What condition is associated with UQCC2 p.Pro75= (c.225C>A)?

UQCC2 p.Pro75= (c.225C>A) is associated with mitochondrial complex III deficiency nuclear type 7 (ClinVar).

How common is UQCC2 p.Pro75= (c.225C>A) in the general population?

UQCC2 p.Pro75= (c.225C>A) is rare (popmax 0.537%, afr) (gnomAD).

UQCC2 p.Pro75=

c.225C>A · rs114881155 · VCV516964

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.537%, afr)

Conditions

mitochondrial complex III deficiency nuclear type 7

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 0.51	GERP -3.9, phastCons 0.99
Overall
CADD	6.785	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.537% African / African-American · 403/75,042 alleles

Filtering AF 0.494% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.477%

Overall 0.0439% 709/1,614,180 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.537%	186
Middle Eastern	0.066%	1,516
Admixed American	0.0416%	2,401
Remaining individualsnot grpmax-eligible	0.0288%	3,473
European (non-Finnish)	0.0208%	4,816
South Asian	0.0121%	8,280
Finnishnot grpmax-eligible	0.00469%	21,345

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: UQCC2
Protein: p.Pro75=
Coding: c.225C>A
MANE Select: NM_032340
dbSNP: rs114881155
Type: single nucleotide variant
Location: chr6:33700502 (GRCh38)
Gene constraint: LOEUF 1.398 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.94

Full UQCC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

mitochondrial complex III deficiency nuclear type 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

UQCC2 c.214-9G>A Uncertain significance ★★ same condition
UQCC2 c.283+3A>C Uncertain significance ★★ same condition
UQCC2 p.Ala2Thr Uncertain significance ★★ ⚠ same condition
UQCC2 p.Ala38Thr Uncertain significance ★★ ⚠ same condition
UQCC2 p.Gln46= Uncertain significance ★★ same condition
UQCC2 p.Arg25= Likely benign ★★ same condition
UQCC2 p.Met107Ile Likely benign ★★ same condition
UQCC2 c.214-6G>A 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/uqcc2-p-pro75 (accessed [today's date]).

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