Is COMMD7 p.Asn168Ser (c.503A>G) pathogenic?

COMMD7 p.Asn168Ser (c.503A>G) is classified Uncertain significance in COMMD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely benign (0.0644); Very rare (popmax 0.000255%, nfe).

How common is COMMD7 p.Asn168Ser (c.503A>G) in the general population?

COMMD7 p.Asn168Ser (c.503A>G) is very rare (popmax 0.000255%, nfe) (gnomAD).

What do computational predictors say about COMMD7 p.Asn168Ser (c.503A>G)?

AlphaMissense predicts likely benign (score 0.0644) — an in-silico prediction, not a clinical call.

COMMD7 p.Asn168Ser

c.503A>G · rs2515106896 · VCV2485288

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0644 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000255%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0644	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -6.25	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 1.9	GERP -0.84, phastCons 1
Regional constraint	o/e 0.87	unconstrained · MANE · 40 kb · p 0.049 · regional, not allelic
Overall
CADD	16.02	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 0.000255% European (non-Finnish) · 3/1,178,214 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000206% 3/1,458,214 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: COMMD7
Protein: p.Asn168Ser
Coding: c.503A>G
MANE Select: NM_053041
dbSNP: rs2515106896
Type: single nucleotide variant
Location: chr20:32704046 (GRCh38)
Gene constraint: LOEUF 1.147 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.76 · 4 PDB
Residue 168: the comm domain

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.Asp18Asn 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-asn168ser (accessed [today's date]).

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