Is COMMD7 p.Glu48Asp (c.144A>C) pathogenic?

COMMD7 p.Glu48Asp (c.144A>C) is classified Uncertain significance in COMMD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely benign (0.1678); Very rare (popmax 0.00446%, eas).

How common is COMMD7 p.Glu48Asp (c.144A>C) in the general population?

COMMD7 p.Glu48Asp (c.144A>C) is very rare (popmax 0.00446%, eas) (gnomAD).

What do computational predictors say about COMMD7 p.Glu48Asp (c.144A>C)?

AlphaMissense predicts likely benign (score 0.1678) — an in-silico prediction, not a clinical call.

COMMD7 p.Glu48Asp

c.144A>C · VCV4232726

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1678 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00446%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1678	likely benign
REVEL	0.166	moderately benign-leaning
SaProt	LLR -5.86	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 -0.54	GERP -2.7
Regional constraint	o/e 0.87	unconstrained · MANE · 40 kb · p 0.049 · regional, not allelic
Overall
CADD	13.94	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 0.00446% East Asian · 2/44,882 alleles

Filtering AF 0.000739% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000276%

Overall 0.000205% 3/1,461,812 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00446%	22,441
Remaining individualsnot grpmax-eligible	0.0016%	62,508

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: COMMD7
Protein: p.Glu48Asp
Coding: c.144A>C
MANE Select: NM_053041
Type: single nucleotide variant
Location: chr20:32727990 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.76 · 4 PDB
Residue 48: an α-helix

Full COMMD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD7 c.526+3G>A Benign ★★ same type
COMMD7 p.Ala117Val Uncertain significance ★ ⚠ same type
COMMD7 p.Ala121Val Uncertain significance ★ ⚠ same type
COMMD7 p.Ala14Ser Uncertain significance ★ ⚠ same type
COMMD7 p.Ala32Asp Uncertain significance ★ ⚠ same type
COMMD7 p.Ala94Val Uncertain significance ★ ⚠ same type
COMMD7 p.Arg122Gly Uncertain significance ★ ⚠ same type
COMMD7 p.Asn168Ser 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/commd7-p-glu48asp (accessed [today's date]).

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