Is COX6A2 p.Pro73= (c.219C>T) pathogenic?

COX6A2 p.Pro73= (c.219C>T) is classified Benign in COX6A2 (ClinVar, Single submitter, 2 submitters; last evaluated 2022-10-27). Common (popmax 11.1%, sas) — too common for a highly-penetrant pathogenic allele.

COX6A2 p.Pro73=

Q: How common is COX6A2 p.Pro73= (c.219C>T) in the general population?

COX6A2 p.Pro73= (c.219C>T) is common (popmax 11.1%, sas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.219C>T · rs12240 · VCV3059761

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 11.1%, sas) — too common for a highly-penetrant pathogenic allele

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 2.4	GERP -1.5, phastCons 1
Overall
CADD	12.02	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 11.1% South Asian · 6,023/54,426 alleles

Filtering AF 10.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.7%

Overall 7.67% 107,573/1,401,918 alleles · common

Ancestry group	Frequency	1 in
South Asiangrpmax	11.1%	9
Amishnot grpmax-eligible	10.7%	9
Finnishnot grpmax-eligible	9.93%	10
African / African-American	8.6%	12
European (non-Finnish)	7.59%	13
Remaining individualsnot grpmax-eligible	7.26%	14
East Asian	6.09%	16
Ashkenazi Jewishnot grpmax-eligible	5.24%	19
Middle Eastern	4.04%	25
Admixed American	3.78%	26

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: COX6A2
Protein: p.Pro73=
Coding: c.219C>T
MANE Select: NM_005205
dbSNP: rs12240
Type: single nucleotide variant
Location: chr16:31427849 (GRCh38)
Gene constraint: LOEUF 1.913 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.30

Full COX6A2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX6A2 p.Leu81Val Uncertain significance ★★ ⚠ same type
COX6A2 p.Ser39Arg Likely pathogenic ★ ⚠ same type
COX6A2 p.Ala2Thr Uncertain significance ★ ⚠ same type
COX6A2 p.Arg54Leu Uncertain significance ★ ⚠ same type
COX6A2 p.Arg60Cys Uncertain significance ★ ⚠ same type
COX6A2 p.Arg66Gly Uncertain significance ★ ⚠ same type
COX6A2 p.Arg68His Uncertain significance ★ ⚠ same type
COX6A2 p.Asn46Ile 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/cox6a2-p-pro73 (accessed [today's date]).

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