Is CP p.Glu544Asp (c.1632A>T) pathogenic?

CP p.Glu544Asp (c.1632A>T) is classified Benign in CP (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-04). AlphaMissense: likely benign (0.0461); Common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele; Associated with aceruloplasminemia.

What condition is associated with CP p.Glu544Asp (c.1632A>T)?

CP p.Glu544Asp (c.1632A>T) is associated with aceruloplasminemia (ClinVar).

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.Glu544Asp (c.1632A>T)?

AlphaMissense predicts likely benign (score 0.0461) — an in-silico prediction, not a clinical call.

CP p.Glu544Asp

Q: How common is CP p.Glu544Asp (c.1632A>T) in the general population?

CP p.Glu544Asp (c.1632A>T) is common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1632A>T · rs701753 · VCV198992

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0461 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 100%, eas) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

aceruloplasminemia

Computational evidence

Protein change
AlphaMissense	0.0461	likely benign
REVEL	0.299	indeterminate
SaProt	LLR -3.85	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.56	GERP -3, phastCons 0.91
Regional constraint	o/e 0.80	unconstrained · MANE · 25 kb · p 2.5e-07 · regional, not allelic
Overall
CADD	5.586	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 100% East Asian · 44,852/44,864 alleles

Filtering AF 99.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 98.9%

Overall 92.5% 1,488,503/1,609,336 alleles · common

Ancestry group	Frequency	1 in
East Asiangrpmax	100%	1
Admixed American	94.9%	1
Finnishnot grpmax-eligible	94.2%	1
Amishnot grpmax-eligible	94.1%	1
European (non-Finnish)	93.9%	1
Ashkenazi Jewishnot grpmax-eligible	93.7%	1
Remaining individualsnot grpmax-eligible	92.3%	1
Middle Eastern	88.8%	1
South Asian	87.3%	1
African / African-American	69.2%	1

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.Glu544Asp
Coding: c.1632A>T
MANE Select: NM_000096
dbSNP: rs701753
Type: single nucleotide variant
Location: chr3:149198448 (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 544: a β-strand; the plastocyanin-like 3 domain; a disulfide bond; a UniProt-annotated variant site (no effect on the localization at the plasma membrane)

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

CP p.Glu544= Benign ★ same residue
CP c.1208+1G>A Pathogenic ★★ same condition
CP c.2879-1G>T Likely pathogenic ★★ same condition
CP p.Arg901Ter Pathogenic ★★ same condition
CP p.Gly195Arg Likely pathogenic ★★ same condition
CP p.Gly650Arg Pathogenic/Likely pathogenic ★★ same condition
CP p.Gly708Ser Pathogenic ★★ same condition
CP p.Leu919Pro Pathogenic/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-glu544asp (accessed [today's date]).

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