Is CP p.Gly172Arg (c.514G>C) pathogenic?

CP p.Gly172Arg (c.514G>C) is classified Conflicting classifications of pathogenicity in CP (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-09-28). AlphaMissense: likely benign (0.1335); Rare (popmax 0.112%, sas); Associated with aceruloplasminemia.

What condition is associated with CP p.Gly172Arg (c.514G>C)?

CP p.Gly172Arg (c.514G>C) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Gly172Arg (c.514G>C) in the general population?

CP p.Gly172Arg (c.514G>C) is rare (popmax 0.112%, 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.Gly172Arg (c.514G>C)?

AlphaMissense predicts likely benign (score 0.1335) — an in-silico prediction, not a clinical call.

CP p.Gly172Arg

c.514G>C · rs768492670 · VCV1383171

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1335 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.112%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

aceruloplasminemia

Computational evidence

Protein change
AlphaMissense	0.1335	likely benign
REVEL	0.302	indeterminate
SaProt	LLR -7.58	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 -0.83	GERP -4.4
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.56 · regional, not allelic
Overall
CADD	0.567	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 0.112% South Asian · 102/91,086 alleles

Filtering AF 0.0944% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0877%

Overall 0.00663% 107/1,613,936 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.112%	893
Admixed American	0.00667%	14,998
Remaining individualsnot grpmax-eligible	0.0016%	62,484

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.Gly172Arg
Coding: c.514G>C
MANE Select: NM_000096
dbSNP: rs768492670
Type: single nucleotide variant
Location: chr3:149210260 (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 172: the plastocyanin-like 1 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-gly172arg (accessed [today's date]).

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