Is CP p.Ile183Thr (c.548T>C) pathogenic?

CP p.Ile183Thr (c.548T>C) is classified Uncertain significance in CP (ClinVar, Single submitter, 2 submitters; last evaluated 2021-11-05). AlphaMissense: likely benign (0.0887); Very rare (popmax 0.00439%, sas); Associated with aceruloplasminemia.

What condition is associated with CP p.Ile183Thr (c.548T>C)?

CP p.Ile183Thr (c.548T>C) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Ile183Thr (c.548T>C) in the general population?

CP p.Ile183Thr (c.548T>C) is very rare (popmax 0.00439%, sas) (gnomAD).

How is Aceruloplasminemia inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about CP p.Ile183Thr (c.548T>C)?

AlphaMissense predicts likely benign (score 0.0887) — an in-silico prediction, not a clinical call.

CP p.Ile183Thr

c.548T>C · rs386134123 · VCV42056

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0887 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00439%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

aceruloplasminemia

Computational evidence

Protein change
AlphaMissense	0.0887	likely benign
REVEL	0.672	pathogenic-leaning
SaProt	LLR -7.84	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.56 · regional, not allelic
Overall
CADD	24.1	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 0.00439% South Asian · 4/91,086 alleles

Filtering AF 0.00307% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00275%

Overall 0.00341% 55/1,613,960 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00439%	22,772
European (non-Finnish)	0.00398%	25,105
Admixed American	0.00333%	29,991
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-American	0.00133%	74,932

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: CP
Protein: p.Ile183Thr
Coding: c.548T>C
MANE Select: NM_000096
dbSNP: rs386134123
Type: single nucleotide variant
Location: chr3:149210226 (GRCh38)
Gene constraint: LOEUF 0.624 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.79 · 4 PDB
Residue 183: the plastocyanin-like 1 domain; a disulfide bond

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

Disease context

aceruloplasminemia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Aceruloplasminemia (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult, Elderly
Prevalence: 1-9 / 1 000 000 (Japan)

Similar variants

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CP p.Gly650Arg Pathogenic/Likely pathogenic ★★ same condition
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CP p.Val219Glu Likely pathogenic ★★ same condition

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/cp-p-ile183thr (accessed [today's date]).

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