Is COMMD5 p.Arg38Gln (c.113G>A) pathogenic?

COMMD5 p.Arg38Gln (c.113G>A) is classified Likely benign in COMMD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-01). AlphaMissense: likely benign (0.0663); Rare (popmax 0.747%, nfe).

How common is COMMD5 p.Arg38Gln (c.113G>A) in the general population?

COMMD5 p.Arg38Gln (c.113G>A) is rare (popmax 0.747%, nfe) (gnomAD).

What do computational predictors say about COMMD5 p.Arg38Gln (c.113G>A)?

AlphaMissense predicts likely benign (score 0.0663) — an in-silico prediction, not a clinical call.

COMMD5 p.Arg38Gln

c.113G>A · rs140849685 · VCV2659001

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0663 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.747%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0663	likely benign
REVEL	0.029	moderately benign-leaning
SaProt	LLR -6.01	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 -0.19	GERP -1.9, phastCons 0.001
Regional constraint	o/e 0.81	unconstrained · MANE · 671 bp · p 0.0015 · regional, not allelic
Overall
CADD	6.324	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 0.747% European (non-Finnish) · 8,818/1,180,034 alleles

Filtering AF 0.734% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.729%

Overall 0.607% 9,803/1,614,012 alleles · rare exomes 9,152/1,461,720 · genomes 651/152,292 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.21%	83
European (non-Finnish)grpmax	0.747%	134
Admixed American	0.651%	154
Remaining individualsnot grpmax-eligible	0.645%	155
African / African-American	0.149%	670
Middle Eastern	0.132%	758
Ashkenazi Jewishnot grpmax-eligible	0.0912%	1,097
Finnishnot grpmax-eligible	0.0392%	2,554
South Asian	0.00878%	11,385

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg38Gln
Coding: c.113G>A
MANE Select: NM_014066
dbSNP: rs140849685
Type: single nucleotide variant
Location: chr8:144851226 (GRCh38)
Gene constraint: LOEUF 1.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.49 · 4 PDB
Residue 38: 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.Arg201Gln 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

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-arg38gln (accessed [today's date]).

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