Is CCDC181 p.Pro294= (c.882A>G) pathogenic?

CCDC181 p.Pro294= (c.882A>G) is classified Likely benign in CCDC181 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-01). Ultra-rare (popmax 0.0174%, afr).

How common is CCDC181 p.Pro294= (c.882A>G) in the general population?

CCDC181 p.Pro294= (c.882A>G) is ultra-rare (popmax 0.0174%, afr) (gnomAD).

CCDC181 p.Pro294=

c.882A>G · rs113005897 · VCV2639534

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0174%, afr)

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 -1.3	GERP -2.1, phastCons 0.001
Overall
CADD	3.788	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0174% African / African-American · 13/74,922 alleles

Filtering AF 0.0103% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00813%

Overall 0.00173% 28/1,614,044 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0208%	4,807
African / African-Americangrpmax	0.0174%	5,763
Admixed American	0.00333%	29,992

Remaining individuals 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: CCDC181
Protein: p.Pro294=
Coding: c.882A>G
MANE Select: NM_001300969
dbSNP: rs113005897
Type: single nucleotide variant
Location: chr1:169421549 (GRCh38)
Gene constraint: LOEUF 0.85 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.92
Residue 294: the 'disordered' region

Full CCDC181 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC181 p.Ala292Thr Uncertain significance ★ ⚠ same type
CCDC181 p.Ala414Pro Uncertain significance ★ ⚠ same type
CCDC181 p.Ala41Val Uncertain significance ★ ⚠ same type
CCDC181 p.Arg150Gln Uncertain significance ★ ⚠ same type
CCDC181 p.Arg298Cys Uncertain significance ★ ⚠ same type
CCDC181 p.Arg310Gln Uncertain significance ★ ⚠ same type
CCDC181 p.Arg395Pro Uncertain significance ★ ⚠ same type
CCDC181 p.Arg416Gln Uncertain significance ★ ⚠ 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/ccdc181-p-pro294 (accessed [today's date]).

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