Is CCDC27 p.Pro211Leu (c.632C>T) pathogenic?

CCDC27 p.Pro211Leu (c.632C>T) is classified Uncertain significance in CCDC27 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-25). AlphaMissense: likely benign (0.1253); Rare (popmax 0.198%, mid).

How common is CCDC27 p.Pro211Leu (c.632C>T) in the general population?

CCDC27 p.Pro211Leu (c.632C>T) is rare (popmax 0.198%, mid) (gnomAD).

What do computational predictors say about CCDC27 p.Pro211Leu (c.632C>T)?

AlphaMissense predicts likely benign (score 0.1253) — an in-silico prediction, not a clinical call.

CCDC27 p.Pro211Leu

c.632C>T · rs754556751 · VCV2241465

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1253 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.198%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1253	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -6.60	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 0.18	GERP 1.2, phastCons 0.003
Regional constraint	o/e 1.01	unconstrained · MANE · 19 kb · p 0.84 · regional, not allelic
Overall
CADD	16.53	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.198% Middle Eastern · 12/6,056 alleles

Filtering AF 0.114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0896%

Overall 0.00508% 82/1,614,006 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.198%	505
East Asian	0.00668%	14,959
African / African-American	0.00666%	15,006
Remaining individualsnot grpmax-eligible	0.0064%	15,625
European (non-Finnish)	0.00483%	20,702
South Asian	0.0011%	91,076

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.Pro211Leu
Coding: c.632C>T
MANE Select: NM_152492
dbSNP: rs754556751
Type: single nucleotide variant
Location: chr1:3756811 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.70

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-pro211leu (accessed [today's date]).

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