Is CP p.Met985Val (c.2953A>G) pathogenic?

CP p.Met985Val (c.2953A>G) is classified Pathogenic in CP (ClinVar, No assertion criteria, 1 submitter; last evaluated 2013-04-18). AlphaMissense: likely benign (0.1125); Absent from gnomAD v4.1; Associated with aceruloplasminemia.

What condition is associated with CP p.Met985Val (c.2953A>G)?

CP p.Met985Val (c.2953A>G) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Met985Val (c.2953A>G) in the general population?

CP p.Met985Val (c.2953A>G) is absent from gnomAD v4.1 (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.Met985Val (c.2953A>G)?

AlphaMissense predicts likely benign (score 0.1125) — an in-silico prediction, not a clinical call.

CP p.Met985Val

c.2953A>G · rs386134132 · VCV42062

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1125 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

aceruloplasminemia

Computational evidence

Protein change
AlphaMissense	0.1125	likely benign ⚠ discordant with ClinVar
REVEL	0.646	pathogenic-leaning
SaProt	LLR -8.43	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 1	GERP -1.9, phastCons 1
Regional constraint	o/e 0.80	unconstrained · MANE · 25 kb · p 2.5e-07 · regional, not allelic
Overall
CADD	19.21	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

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: CP
Protein: p.Met985Val
Coding: c.2953A>G
MANE Select: NM_000096
dbSNP: rs386134132
Type: single nucleotide variant
Location: chr3:149177905 (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 985: a β-strand; the plastocyanin-like 6 domain

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 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
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-met985val (accessed [today's date]).

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