Is COMMD6 p.Asp33Asn (c.97G>A) pathogenic?

COMMD6 p.Asp33Asn (c.97G>A) is classified Uncertain significance in COMMD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-09). AlphaMissense: likely benign (0.1695); Ultra-rare (popmax 0.0823%, mid).

How common is COMMD6 p.Asp33Asn (c.97G>A) in the general population?

COMMD6 p.Asp33Asn (c.97G>A) is ultra-rare (popmax 0.0823%, mid) (gnomAD).

What do computational predictors say about COMMD6 p.Asp33Asn (c.97G>A)?

AlphaMissense predicts likely benign (score 0.1695) — an in-silico prediction, not a clinical call.

COMMD6 p.Asp33Asn

c.97G>A · rs149125057 · VCV2225942

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1695 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0823%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1695	likely benign
REVEL	0.194	benign-leaning
SaProt	LLR -10.77	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.4	GERP 0.58, phastCons 0.78
Regional constraint	o/e 1.21	unconstrained · MANE · 11 kb · p 0.033 · regional, not allelic
Overall
CADD	23.7	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 0.0823% Middle Eastern · 5/6,072 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00527% 85/1,613,598 alleles · ultra-rare exomes 78/1,461,418 · genomes 7/152,180 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0823%	1,214
Admixed American	0.0117%	8,562
Remaining individualsnot grpmax-eligible	0.008%	12,494
European (non-Finnish)	0.00559%	17,876
African / African-American	0.00267%	37,458

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: COMMD6
Protein: p.Asp33Asn
Coding: c.97G>A
MANE Select: NM_203495
dbSNP: rs149125057
Type: single nucleotide variant
Location: chr13:75530224 (GRCh38)
Gene constraint: LOEUF 1.538 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 85.37 · 3 PDB
Residue 33: the comm domain; a β-strand

Full COMMD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD6 p.Ala50Pro Uncertain significance ★ ⚠ same type
COMMD6 p.Ile82Thr Uncertain significance ★ ⚠ same type
COMMD6 p.Lys57Asn Uncertain significance ★ ⚠ same type
COMMD6 p.Met28Val Uncertain significance ★ ⚠ same type
COMMD6 p.Met46Ile Uncertain significance ★ ⚠ same type
COMMD6 p.Phe61Ser Uncertain significance ★ ⚠ same type
COMMD6 p.Val30Met 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/commd6-p-asp33asn (accessed [today's date]).

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