Is CCDC27 p.Pro390= (c.1170G>A) pathogenic?

CCDC27 p.Pro390= (c.1170G>A) is classified Likely benign in CCDC27 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-01). Rare (popmax 0.708%, afr).

How common is CCDC27 p.Pro390= (c.1170G>A) in the general population?

CCDC27 p.Pro390= (c.1170G>A) is rare (popmax 0.708%, afr) (gnomAD).

CCDC27 p.Pro390=

c.1170G>A · rs141116417 · VCV2638106

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.708%, 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 -0.45	GERP -4.3
Overall
CADD	5.281	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.708% African / African-American · 531/74,980 alleles

Filtering AF 0.658% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.639%

Overall 0.447% 7,203/1,611,994 alleles · rare

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	1.21%	83
African / African-Americangrpmax	0.708%	141
European (non-Finnish)	0.509%	196
Admixed American	0.426%	235
Remaining individualsnot grpmax-eligible	0.386%	259
Finnishnot grpmax-eligible	0.158%	633
Ashkenazi Jewishnot grpmax-eligible	0.142%	703
Middle Eastern	0.0906%	1,104
East Asian	0.0134%	7,474
South Asian	0.0055%	18,172

Amish 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: CCDC27
Protein: p.Pro390=
Coding: c.1170G>A
MANE Select: NM_152492
dbSNP: rs141116417
Type: single nucleotide variant
Location: chr1:3763323 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.70
Residue 390: a UniProt-annotated variant site (in); the 'disordered' region

Full CCDC27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC27 p.Ala112Pro Uncertain significance ★ ⚠ same type
CCDC27 p.Ala112Val Uncertain significance ★ ⚠ same type
CCDC27 p.Ala153Val Uncertain significance ★ ⚠ same type
CCDC27 p.Ala293Thr Uncertain significance ★ ⚠ same type
CCDC27 p.Ala324Val Uncertain significance ★ ⚠ same type
CCDC27 p.Ala574Val Uncertain significance ★ ⚠ same type
CCDC27 p.Ala78Asp Uncertain significance ★ ⚠ same type
CCDC27 p.Ala78Thr 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/ccdc27-p-pro390 (accessed [today's date]).

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