Is COMMD1 p.Glu5Asp (c.15G>C) pathogenic?

COMMD1 p.Glu5Asp (c.15G>C) is classified Uncertain significance in COMMD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-01). AlphaMissense: likely benign (0.0742); Ultra-rare (popmax 0.0277%, amr).

How common is COMMD1 p.Glu5Asp (c.15G>C) in the general population?

COMMD1 p.Glu5Asp (c.15G>C) is ultra-rare (popmax 0.0277%, amr) (gnomAD).

What do computational predictors say about COMMD1 p.Glu5Asp (c.15G>C)?

AlphaMissense predicts likely benign (score 0.0742) — an in-silico prediction, not a clinical call.

COMMD1 p.Glu5Asp

c.15G>C · rs766788858 · VCV2217999

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0742 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0277%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0742	likely benign
REVEL	0.079	moderately benign-leaning
SaProt	LLR -6.16	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 0.24	GERP -0.49, phastCons 0.002
Regional constraint	o/e 1.17	unconstrained · MANE · 230 kb · p 0.012 · regional, not allelic
Overall
CADD	9.139	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 0.0277% Admixed American · 15/54,244 alleles

Filtering AF 0.017% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00153% 24/1,572,756 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0277%	3,616
Remaining individualsnot grpmax-eligible	0.00494%	20,243
African / African-American	0.00404%	24,769
South Asian	0.00344%	29,111

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: COMMD1
Protein: p.Glu5Asp
Coding: c.15G>C
MANE Select: NM_152516
dbSNP: rs766788858
Type: single nucleotide variant
Location: chr2:61905693 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.58 · 4 PDB
Residue 5: a turn; the 'sufficient for interaction with slc12a2' region

Full COMMD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD1 p.Asn111Ile Uncertain significance ★ ⚠ same type
COMMD1 p.Asn190Asp Uncertain significance ★ ⚠ same type
COMMD1 p.Gln131His Uncertain significance ★ ⚠ same type
COMMD1 p.Gln137Glu Uncertain significance ★ ⚠ same type
COMMD1 p.Glu148Asp Uncertain significance ★ ⚠ same type
COMMD1 p.Glu33Val Uncertain significance ★ ⚠ same type
COMMD1 p.Gly121Asp Uncertain significance ★ ⚠ same type
COMMD1 p.His101Gln 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/commd1-p-glu5asp (accessed [today's date]).

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