Is COMMD7 p.Glu138Ala (c.413A>C) pathogenic?

COMMD7 p.Glu138Ala (c.413A>C) is classified Uncertain significance in COMMD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-04). AlphaMissense: ambiguous (0.4634); Absent from gnomAD v4.1.

How common is COMMD7 p.Glu138Ala (c.413A>C) in the general population?

COMMD7 p.Glu138Ala (c.413A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COMMD7 p.Glu138Ala (c.413A>C)?

AlphaMissense predicts ambiguous (score 0.4634) — an in-silico prediction, not a clinical call.

COMMD7 p.Glu138Ala

c.413A>C · VCV4005700

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4634 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4634	ambiguous
REVEL	0.282	benign-leaning
SaProt	LLR -12.36	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 7.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 40 kb · p 0.049 · regional, not allelic
Overall
CADD	27.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: COMMD7
Protein: p.Glu138Ala
Coding: c.413A>C
MANE Select: NM_053041
Type: single nucleotide variant
Location: chr20:32704828 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.76 · 4 PDB
Residue 138: the comm domain; a β-strand

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-glu138ala (accessed [today's date]).

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