Is COX7B p.Ser7= (c.21C>T) pathogenic?

COX7B p.Ser7= (c.21C>T) is classified Likely benign in COX7B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-22). Ultra-rare (popmax 0.0143%, nfe).

How common is COX7B p.Ser7= (c.21C>T) in the general population?

COX7B p.Ser7= (c.21C>T) is ultra-rare (popmax 0.0143%, nfe) (gnomAD).

COX7B p.Ser7=

c.21C>T · VCV3622754

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0143%, nfe)

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 -0.053	GERP -1.2, phastCons 0.58
Overall
CADD	7.995	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0143% European (non-Finnish) · 128/894,807 alleles

Filtering AF 0.0122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0115%

Overall 0.0109% 132/1,208,803 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0143%	6,991
Remaining individualsnot grpmax-eligible	0.00421%	23,780
African / African-American	0.00351%	28,476

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: COX7B
Protein: p.Ser7=
Coding: c.21C>T
MANE Select: NM_001866
Type: single nucleotide variant
Location: chrX:77899574 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 3 PDB

Full COX7B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX7B p.Ser7Arg Conflicting classifications of pathogenicity ★ ⚠ same residue
COX7B p.Arg29His Uncertain significance ★★ ⚠ same type
COX7B c.165+10A>G Benign ★★ same type
COX7B c.*82G>T Likely benign ★★ same type
COX7B p.Ser16Arg Benign ★★ same type
COX7B c.40+5G>C Likely pathogenic ★ same type
COX7B p.Ala57Ser Uncertain significance ★ ⚠ same type
COX7B p.Asn79Asp 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/cox7b-p-ser7 (accessed [today's date]).

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