Is COMMD8 p.Gln116Arg (c.347A>G) pathogenic?

COMMD8 p.Gln116Arg (c.347A>G) is classified Uncertain significance in COMMD8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-19). AlphaMissense: likely benign (0.134); Very rare (popmax 0.00263%, nfe).

How common is COMMD8 p.Gln116Arg (c.347A>G) in the general population?

COMMD8 p.Gln116Arg (c.347A>G) is very rare (popmax 0.00263%, nfe) (gnomAD).

What do computational predictors say about COMMD8 p.Gln116Arg (c.347A>G)?

AlphaMissense predicts likely benign (score 0.134) — an in-silico prediction, not a clinical call.

COMMD8 p.Gln116Arg

c.347A>G · VCV4655804

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.134 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00263%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.134	likely benign
REVEL	0.054	moderately benign-leaning
SaProt	LLR -7.92	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 12 kb · p 0.69 · regional, not allelic
Overall
CADD	19.93	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00263% European (non-Finnish) · 31/1,177,978 alleles

Filtering AF 0.00189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00164%

Overall 0.00199% 32/1,608,034 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00263%	37,999
Remaining individualsnot grpmax-eligible	0.00161%	62,200

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: COMMD8
Protein: p.Gln116Arg
Coding: c.347A>G
MANE Select: NM_017845
Type: single nucleotide variant
Location: chr4:47456605 (GRCh38)
Gene constraint: LOEUF 1.369 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.67 · 3 PDB
Residue 116: the comm domain; a β-strand

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.Arg97Gly Uncertain significance ★ same type
COMMD8 p.Asp131Glu 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-gln116arg (accessed [today's date]).

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