Is COMMD5 p.Arg201Gln (c.602G>A) pathogenic?

COMMD5 p.Arg201Gln (c.602G>A) is classified Uncertain significance in COMMD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-09). AlphaMissense: ambiguous (0.4709); Ultra-rare (popmax 0.0213%, afr).

How common is COMMD5 p.Arg201Gln (c.602G>A) in the general population?

COMMD5 p.Arg201Gln (c.602G>A) is ultra-rare (popmax 0.0213%, afr) (gnomAD).

What do computational predictors say about COMMD5 p.Arg201Gln (c.602G>A)?

AlphaMissense predicts ambiguous (score 0.4709) — an in-silico prediction, not a clinical call.

COMMD5 p.Arg201Gln

c.602G>A · rs141500693 · VCV2212768

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4709 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4709	ambiguous
REVEL	0.231	benign-leaning
SaProt	LLR -10.78	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.8	GERP 1.7, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 671 bp · p 0.0015 · regional, not allelic
Overall
CADD	27.0	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 0.0213% African / African-American · 16/75,046 alleles

Filtering AF 0.0133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0109%

Overall 0.0018% 29/1,614,162 alleles · ultra-rare exomes 18/1,461,836 · genomes 11/152,326 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0213%	4,690
Finnishnot grpmax-eligible	0.00469%	21,331
Remaining individualsnot grpmax-eligible	0.0032%	31,255
South Asian	0.0011%	91,088
European (non-Finnish)	0.000593%	168,579

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: COMMD5
Protein: p.Arg201Gln
Coding: c.602G>A
MANE Select: NM_014066
dbSNP: rs141500693
Type: single nucleotide variant
Location: chr8:144850737 (GRCh38)
Gene constraint: LOEUF 1.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.49 · 4 PDB
Residue 201: the comm domain; an α-helix

Full COMMD5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD5 p.Ala153Thr Uncertain significance ★ ⚠ same type
COMMD5 p.Arg135Gln Uncertain significance ★ ⚠ same type
COMMD5 p.Arg158Trp Uncertain significance ★ ⚠ same type
COMMD5 p.Arg217Ser Uncertain significance ★ ⚠ same type
COMMD5 p.Arg220His Uncertain significance ★ ⚠ same type
COMMD5 p.Arg65Gln Uncertain significance ★ ⚠ same type
COMMD5 p.Arg70His Uncertain significance ★ ⚠ same type
COMMD5 p.Asn76Ser 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/commd5-p-arg201gln (accessed [today's date]).

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