Is COMMD8 p.Arg97Gly (c.289A>G) pathogenic?

COMMD8 p.Arg97Gly (c.289A>G) is classified Uncertain significance in COMMD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-03-06). AlphaMissense: likely pathogenic (0.8866); Absent from gnomAD v4.1.

How common is COMMD8 p.Arg97Gly (c.289A>G) in the general population?

COMMD8 p.Arg97Gly (c.289A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COMMD8 p.Arg97Gly (c.289A>G)?

AlphaMissense predicts likely pathogenic (score 0.8866) — an in-silico prediction, not a clinical call.

COMMD8 p.Arg97Gly

c.289A>G · VCV4967073

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8866 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,609,790)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8866	likely pathogenic · top 4% in COMMD8
REVEL	0.37	indeterminate
SaProt	LLR -15.10	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 4.3	GERP -0.63, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 12 kb · p 0.69 · regional, not allelic
Overall
CADD	24.7	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

No allele count reported in gnomAD v4.1 (AN 1,609,790). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: COMMD8
Protein: p.Arg97Gly
Coding: c.289A>G
MANE Select: NM_017845
Type: single nucleotide variant
Location: chr4:47456663 (GRCh38)
Gene constraint: LOEUF 1.369 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 3 PDB
Residue 97: an α-helix

Full COMMD8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD8 p.Trp122Gly Uncertain significance ★★ ⚠ same type
COMMD8 p.Arg11Gln Uncertain significance ★ ⚠ same type
COMMD8 p.Asp131Glu Uncertain significance ★ ⚠ same type
COMMD8 p.Gln116Arg Uncertain significance ★ ⚠ same type
COMMD8 p.Glu108Asp Uncertain significance ★ ⚠ same type
COMMD8 p.Glu164Gly Uncertain significance ★ ⚠ same type
COMMD8 p.Glu47Val Uncertain significance ★ ⚠ same type
COMMD8 p.Gly30Asp 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/commd8-p-arg97gly (accessed [today's date]).

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