Is COX7C p.Arg7Trp (c.19C>T) pathogenic?

COX7C p.Arg7Trp (c.19C>T) is classified Uncertain significance in COX7C (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-21). AlphaMissense: likely pathogenic (0.5958); Very rare (popmax 0.005%, amr).

How common is COX7C p.Arg7Trp (c.19C>T) in the general population?

COX7C p.Arg7Trp (c.19C>T) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about COX7C p.Arg7Trp (c.19C>T)?

AlphaMissense predicts likely pathogenic (score 0.5958) — an in-silico prediction, not a clinical call.

COX7C p.Arg7Trp

c.19C>T · VCV3496149

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5958 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.5958	likely pathogenic
REVEL	0.351	indeterminate
SaProt	LLR -12.73	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP 2.1, phastCons 0.95
Regional constraint	o/e 0.73	unconstrained · MANE · 1,410 bp · p 0.022 · regional, not allelic
Overall
CADD	25.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,996 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.00124% 20/1,613,788 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,999
Remaining individualsnot grpmax-eligible	0.0048%	20,819
European (non-Finnish)	0.00119%	84,288

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: COX7C
Protein: p.Arg7Trp
Coding: c.19C>T
MANE Select: NM_001867
Type: single nucleotide variant
Location: chr5:86618074 (GRCh38)
Gene constraint: LOEUF 1.016 · pLI 0.66 (gnomAD)
Structure: AlphaFold pLDDT 91.28 · 3 PDB

Full COX7C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COX7C p.Cys42Tyr Uncertain significance ★ ⚠ same type
COX7C p.Thr51Ile Uncertain significance ★ ⚠ same type
COX7C p.Val55Ile Likely benign ★ ⚠ 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/cox7c-p-arg7trp (accessed [today's date]).

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