Is CCDC27 p.Pro22Ser (c.64C>T) pathogenic?

CCDC27 p.Pro22Ser (c.64C>T) is classified Likely benign in CCDC27 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-02). AlphaMissense: likely benign (0.1025); Ultra-rare (popmax 0.0178%, eas).

How common is CCDC27 p.Pro22Ser (c.64C>T) in the general population?

CCDC27 p.Pro22Ser (c.64C>T) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about CCDC27 p.Pro22Ser (c.64C>T)?

AlphaMissense predicts likely benign (score 0.1025) — an in-silico prediction, not a clinical call.

CCDC27 p.Pro22Ser

c.64C>T · rs759278758 · VCV2615170

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1025 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1025	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -5.77	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.24	GERP -3.4
Regional constraint	o/e 1.01	unconstrained · MANE · 19 kb · p 0.84 · regional, not allelic
Overall
CADD	6.231	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 0.0178% East Asian · 8/44,900 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.00062% 10/1,614,068 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,612
Remaining individualsnot grpmax-eligible	0.0032%	31,244

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.Pro22Ser
Coding: c.64C>T
MANE Select: NM_152492
dbSNP: rs759278758
Type: single nucleotide variant
Location: chr1:3752545 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.70
Residue 22: 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-pro22ser (accessed [today's date]).

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