Is COMMD2 p.Arg29Leu (c.86G>T) pathogenic?

COMMD2 p.Arg29Leu (c.86G>T) is classified Uncertain significance in COMMD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-11-18). AlphaMissense: likely pathogenic (0.7245); Very rare (popmax 6.84e-05%).

How common is COMMD2 p.Arg29Leu (c.86G>T) in the general population?

COMMD2 p.Arg29Leu (c.86G>T) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about COMMD2 p.Arg29Leu (c.86G>T)?

AlphaMissense predicts likely pathogenic (score 0.7245) — an in-silico prediction, not a clinical call.

COMMD2 p.Arg29Leu

c.86G>T · rs1208591847 · VCV2327427

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7245 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7245	likely pathogenic
REVEL	0.123	moderately benign-leaning
SaProt	LLR -8.71	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 11 kb · p 0.52 · regional, not allelic
Overall
CADD	25.9	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

Grpmax group 6.84e-05%

Overall 6.84e-05% 1/1,461,814 alleles · very rare

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: COMMD2
Protein: p.Arg29Leu
Coding: c.86G>T
MANE Select: NM_016094
dbSNP: rs1208591847
Type: single nucleotide variant
Location: chr3:149752269 (GRCh38)
Gene constraint: LOEUF 1.611 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.00 · 3 PDB
Residue 29: an α-helix

Full COMMD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD2 p.Arg29Trp Uncertain significance ★ ⚠ same residue
COMMD2 p.Ala118Val Uncertain significance ★ ⚠ same type
COMMD2 p.Ala136Thr Uncertain significance ★ ⚠ same type
COMMD2 p.Ala170Thr Uncertain significance ★ ⚠ same type
COMMD2 p.Arg130Gln Uncertain significance ★ ⚠ same type
COMMD2 p.Arg196His Uncertain significance ★ ⚠ same type
COMMD2 p.Arg196Leu Uncertain significance ★ ⚠ same type
COMMD2 p.Asn40Thr 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/commd2-p-arg29leu (accessed [today's date]).

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