Is COX7B p.Thr73Ile (c.218C>T) pathogenic?

COX7B p.Thr73Ile (c.218C>T) is classified Uncertain significance in COX7B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-20). AlphaMissense: likely benign (0.1333); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with COX7B p.Thr73Ile (c.218C>T)?

COX7B p.Thr73Ile (c.218C>T) is associated with Inborn genetic diseases (ClinVar).

How common is COX7B p.Thr73Ile (c.218C>T) in the general population?

COX7B p.Thr73Ile (c.218C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COX7B p.Thr73Ile (c.218C>T)?

AlphaMissense predicts likely benign (score 0.1333) — an in-silico prediction, not a clinical call.

COX7B p.Thr73Ile

c.218C>T · VCV3835725

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1333 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1333	likely benign
REVEL	0.183	benign-leaning
SaProt	LLR -11.52	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.7	GERP 2.3, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 5,704 bp · p 0.27 · regional, not allelic
Overall
CADD	22.5	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COX7B
Protein: p.Thr73Ile
Coding: c.218C>T
MANE Select: NM_001866
Type: single nucleotide variant
Location: chrX:77905236 (GRCh38)
Structure: AlphaFold pLDDT 90.15 · 3 PDB

Full COX7B 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

COX7B p.Thr73Ala Uncertain significance ★ ⚠ same residue
COX7B p.Leu66Val Uncertain significance ★ ⚠ same condition
COX7B p.Lys36Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
COX7B p.Ser7Arg Conflicting classifications of pathogenicity ★ ⚠ same condition
COX7B p.Thr54Ala Conflicting classifications of pathogenicity ★ ⚠ same condition
COX7B p.Arg29Cys Likely benign ★ ⚠ same condition
COX7B p.Lys6Arg Likely benign ★ same condition
COX7B p.Arg29His 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-thr73ile (accessed [today's date]).

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