Is COMMD1 p.Ser183Ile (c.548G>T) pathogenic?

COMMD1 p.Ser183Ile (c.548G>T) is classified Uncertain significance in COMMD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-05). AlphaMissense: likely benign (0.1405); Very rare (popmax 0.00361%, nfe).

How common is COMMD1 p.Ser183Ile (c.548G>T) in the general population?

COMMD1 p.Ser183Ile (c.548G>T) is very rare (popmax 0.00361%, nfe) (gnomAD).

What do computational predictors say about COMMD1 p.Ser183Ile (c.548G>T)?

AlphaMissense predicts likely benign (score 0.1405) — an in-silico prediction, not a clinical call.

COMMD1 p.Ser183Ile

c.548G>T · rs770802167 · VCV2512627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1405 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00361%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1405	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -10.40	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 0.16	GERP -3.6, phastCons 0.027
Regional constraint	o/e 1.17	unconstrained · MANE · 230 kb · p 0.012 · regional, not allelic
Overall
CADD	12.71	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 0.00361% European (non-Finnish) · 42/1,162,808 alleles

Filtering AF 0.0027% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0024%

Overall 0.0027% 43/1,595,088 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00361%	27,686
Remaining individualsnot grpmax-eligible	0.00162%	61,854

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: COMMD1
Protein: p.Ser183Ile
Coding: c.548G>T
MANE Select: NM_152516
dbSNP: rs770802167
Type: single nucleotide variant
Location: chr2:62135916 (GRCh38)
Gene constraint: LOEUF 1.116 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 86.58 · 4 PDB
Residue 183: the comm domain; an α-helix; the 'required for binding to ptdins(4,5)p2' region

Full COMMD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COMMD1 p.Asn111Ile Uncertain significance ★ ⚠ same type
COMMD1 p.Asn190Asp Uncertain significance ★ ⚠ same type
COMMD1 p.Gln131His Uncertain significance ★ ⚠ same type
COMMD1 p.Gln137Glu Uncertain significance ★ ⚠ same type
COMMD1 p.Glu148Asp Uncertain significance ★ ⚠ same type
COMMD1 p.Glu33Val Uncertain significance ★ ⚠ same type
COMMD1 p.Glu5Asp Uncertain significance ★ ⚠ same type
COMMD1 p.Gly121Asp 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/commd1-p-ser183ile (accessed [today's date]).

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