Is CCP110 p.Ala433= (c.1299G>A) pathogenic?

CCP110 p.Ala433= (c.1299G>A) is classified Benign in CCP110 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2016-03-28). Common (popmax 20%, mid) — too common for a highly-penetrant pathogenic allele.

CCP110 p.Ala433=

Q: How common is CCP110 p.Ala433= (c.1299G>A) in the general population?

CCP110 p.Ala433= (c.1299G>A) is common (popmax 20%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1299G>A · rs7191012 · VCV402514

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 20%, mid) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.058	GERP -5.5
Overall
CADD	1.607	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 20% Middle Eastern · 1,214/6,062 alleles

Filtering AF 19.1% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.7%

Overall 15% 242,133/1,614,030 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	20.2%	5
Middle Easterngrpmax	20%	5
Admixed American	19.1%	5
East Asian	17.8%	6
African / African-American	15.5%	6
Remaining individualsnot grpmax-eligible	15.4%	6
European (non-Finnish)	15.2%	7
Finnishnot grpmax-eligible	11.5%	9
Amishnot grpmax-eligible	10.7%	9
South Asian	8.58%	12

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala433=
Coding: c.1299G>A
MANE Select: NM_001323572
dbSNP: rs7191012
Type: single nucleotide variant
Location: chr16:19536968 (GRCh38)
Gene constraint: LOEUF 0.372 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 55.11
Residue 433: the 'interaction with cep76' region

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

Similar variants

CCP110 p.Ala433Val Uncertain significance ★ ⚠ same residue
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
CCP110 p.Thr122= 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-ala433 (accessed [today's date]).

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