Is CCP110 p.Pro393Arg (c.1178C>G) pathogenic?

CCP110 p.Pro393Arg (c.1178C>G) is classified Uncertain significance in CCP110 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-20). AlphaMissense: likely pathogenic (0.8146); Very rare (popmax 6.84e-05%).

How common is CCP110 p.Pro393Arg (c.1178C>G) in the general population?

CCP110 p.Pro393Arg (c.1178C>G) is very rare (popmax 6.84e-05%) (gnomAD).

What do computational predictors say about CCP110 p.Pro393Arg (c.1178C>G)?

AlphaMissense predicts likely pathogenic (score 0.8146) — an in-silico prediction, not a clinical call.

CCP110 p.Pro393Arg

c.1178C>G · VCV4222234

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8146 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.84e-05%)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8146	likely pathogenic · top 5% in CCP110
REVEL	0.301	indeterminate
SaProt	LLR -6.78	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 2.9, phastCons 1
Overall
CADD	25.5	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 6.84e-05%

Overall 6.84e-05% 1/1,461,818 alleles · very rare

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: CCP110
Protein: p.Pro393Arg
Coding: c.1178C>G
MANE Select: NM_001323572
Type: single nucleotide variant
Location: chr16:19536847 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.11
Residue 393: the 'interaction with cep76' region

Full CCP110 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCP110 p.Pro393Thr Uncertain significance ★ ⚠ same residue
CCP110 p.Ala433= Benign ★★ same type
CCP110 p.Arg845= Benign ★★ same type
CCP110 p.Asn740= Benign ★★ same type
CCP110 p.Ile252Met Benign ★★ same type
CCP110 p.Lys583= Benign ★★ same type
CCP110 p.Met375Ile Benign ★★ same type
CCP110 p.Pro171Leu Benign ★★ same type

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/ccp110-p-pro393arg (accessed [today's date]).

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