Is CP p.Pro116His (c.347C>A) pathogenic?

CP p.Pro116His (c.347C>A) is classified Benign/Likely benign in CP (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-27). AlphaMissense: ambiguous (0.3401); Low-frequency (popmax 2.02%, afr); Associated with aceruloplasminemia.

What condition is associated with CP p.Pro116His (c.347C>A)?

CP p.Pro116His (c.347C>A) is associated with aceruloplasminemia (ClinVar).

How common is CP p.Pro116His (c.347C>A) in the general population?

CP p.Pro116His (c.347C>A) is low-frequency (popmax 2.02%, afr) (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.Pro116His (c.347C>A)?

AlphaMissense predicts ambiguous (score 0.3401) — an in-silico prediction, not a clinical call.

CP p.Pro116His

c.347C>A · rs73866999 · VCV343787

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

ambiguous

0.3401 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.02%, afr)

Conditions

aceruloplasminemia

Computational evidence

Protein change
AlphaMissense	0.3401	ambiguous
REVEL	0.49	indeterminate
SaProt	LLR -11.01	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 23 kb · p 0.56 · regional, not allelic
Overall
CADD	24.2	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 2.02% African / African-American · 1,514/74,970 alleles

Filtering AF 1.93% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9%

Overall 0.104% 1,676/1,613,804 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	2.02%	50
Remaining individualsnot grpmax-eligible	0.13%	772
Admixed American	0.122%	822
Middle Eastern	0.0165%	6,056
South Asian	0.0011%	91,066
European (non-Finnish)	0.000509%	196,648

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.Pro116His
Coding: c.347C>A
MANE Select: NM_000096
dbSNP: rs73866999
Type: single nucleotide variant
Location: chr3:149212498 (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 116: 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-pro116his (accessed [today's date]).

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