Is COMMD5 p.Leu40Val (c.118C>G) pathogenic?

COMMD5 p.Leu40Val (c.118C>G) is classified Uncertain significance in COMMD5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-31). AlphaMissense: likely benign (0.0941); Absent from gnomAD v4.1.

How common is COMMD5 p.Leu40Val (c.118C>G) in the general population?

COMMD5 p.Leu40Val (c.118C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about COMMD5 p.Leu40Val (c.118C>G)?

AlphaMissense predicts likely benign (score 0.0941) — an in-silico prediction, not a clinical call.

COMMD5 p.Leu40Val

c.118C>G · rs2537761103 · VCV3147916

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0941 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0941	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -4.51	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 2.4	GERP -0.81, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 671 bp · p 0.0015 · regional, not allelic
Overall
CADD	12.7	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

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: COMMD5
Protein: p.Leu40Val
Coding: c.118C>G
MANE Select: NM_014066
dbSNP: rs2537761103
Type: single nucleotide variant
Location: chr8:144851221 (GRCh38)
Gene constraint: LOEUF 1.752 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.49 · 4 PDB
Residue 40: 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-leu40val (accessed [today's date]).

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