Is COMMD10 p.Lys182Met (c.545A>T) pathogenic?

COMMD10 p.Lys182Met (c.545A>T) is classified Uncertain significance in COMMD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-05). AlphaMissense: likely benign (0.1977); Ultra-rare (popmax 0.0121%, afr).

How common is COMMD10 p.Lys182Met (c.545A>T) in the general population?

COMMD10 p.Lys182Met (c.545A>T) is ultra-rare (popmax 0.0121%, afr) (gnomAD).

What do computational predictors say about COMMD10 p.Lys182Met (c.545A>T)?

AlphaMissense predicts likely benign (score 0.1977) — an in-silico prediction, not a clinical call.

COMMD10 p.Lys182Met

c.545A>T · VCV4232703

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1977 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0121%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1977	likely benign
REVEL	0.09	moderately benign-leaning
SaProt	LLR -9.20	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 9.3	GERP 2.4, phastCons 1
Regional constraint	o/e 1.33	unconstrained · MANE · 207 kb · p 5.3e-07 · regional, not allelic
Overall
CADD	24.0	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 0.0121% African / African-American · 9/74,594 alleles

Filtering AF 0.00626% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00469%

Overall 0.000625% 10/1,600,732 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0121%	8,288
Remaining individualsnot grpmax-eligible	0.00161%	62,006

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: COMMD10
Protein: p.Lys182Met
Coding: c.545A>T
MANE Select: NM_016144
Type: single nucleotide variant
Location: chr5:116291551 (GRCh38)
Gene constraint: LOEUF 1.81 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.19 · 6 PDB
Residue 182: an α-helix; the comm domain

Full COMMD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD10 p.Ala196Thr Uncertain significance ★ ⚠ same type
COMMD10 p.Ala2Pro Uncertain significance ★ ⚠ same type
COMMD10 p.Ala5Thr Uncertain significance ★ ⚠ same type
COMMD10 p.Ala90Val Uncertain significance ★ ⚠ same type
COMMD10 p.Arg125Gln Uncertain significance ★ ⚠ same type
COMMD10 p.Arg125Trp Uncertain significance ★ ⚠ same type
COMMD10 p.Arg36Trp Uncertain significance ★ ⚠ same type
COMMD10 p.Asn166Lys 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/commd10-p-lys182met (accessed [today's date]).

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