Is COX6B1 p.Pro83= (c.249C>T) pathogenic?

COX6B1 p.Pro83= (c.249C>T) is classified Likely benign in COX6B1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-12-10). Ultra-rare (popmax 0.0201%, eas); Associated with Inborn genetic diseases.

What condition is associated with COX6B1 p.Pro83= (c.249C>T)?

COX6B1 p.Pro83= (c.249C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COX6B1 p.Pro83= (c.249C>T) in the general population?

COX6B1 p.Pro83= (c.249C>T) is ultra-rare (popmax 0.0201%, eas) (gnomAD).

COX6B1 p.Pro83=

c.249C>T · rs374405819 · VCV507939

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0201%, eas)

Conditions

Inborn genetic diseases

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 0.031	GERP -1.8, phastCons 0.97
Overall
CADD	12.11	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0201% East Asian · 9/44,882 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00779%

Overall 0.00502% 81/1,613,864 alleles · ultra-rare exomes 73/1,461,738 · genomes 8/152,126 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0201%	4,987
European (non-Finnish)	0.00551%	18,153
Remaining individualsnot grpmax-eligible	0.0048%	20,826
Admixed American	0.00333%	29,989
African / African-American	0.00133%	74,918
South Asian	0.0011%	91,082

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: COX6B1
Protein: p.Pro83=
Coding: c.249C>T
MANE Select: NM_001863
dbSNP: rs374405819
Type: single nucleotide variant
Location: chr19:35658635 (GRCh38)
Gene constraint: LOEUF 0.421 · pLI 0.99 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 95.15 · 3 PDB

Full COX6B1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

COX6B1 p.Pro83Ser Uncertain significance ★★ ⚠ same residue
COX6B1 p.Glu55Lys Uncertain significance ★★ ⚠ same condition
COX6B1 p.Glu6Asp Uncertain significance ★★ ⚠ same condition
COX6B1 p.Met5Leu Uncertain significance ★★ ⚠ same condition
COX6B1 p.Val53Met Uncertain significance ★★ ⚠ same condition
COX6B1 p.Ala46Thr Conflicting classifications of pathogenicity ★ ⚠ same condition
COX6B1 p.Leu64Val Uncertain significance ★ ⚠ same condition
COX6B1 p.Thr67Ile Conflicting classifications of pathogenicity ★ ⚠ 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/cox6b1-p-pro83 (accessed [today's date]).

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