Is CCDC27 p.Ala112Pro (c.334G>C) pathogenic?

CCDC27 p.Ala112Pro (c.334G>C) is classified Uncertain significance in CCDC27 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-24). AlphaMissense: likely benign (0.1138); Ultra-rare (popmax 0.0103%, nfe).

How common is CCDC27 p.Ala112Pro (c.334G>C) in the general population?

CCDC27 p.Ala112Pro (c.334G>C) is ultra-rare (popmax 0.0103%, nfe) (gnomAD).

What do computational predictors say about CCDC27 p.Ala112Pro (c.334G>C)?

AlphaMissense predicts likely benign (score 0.1138) — an in-silico prediction, not a clinical call.

CCDC27 p.Ala112Pro

c.334G>C · VCV3828576

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1138 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1138	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -6.18	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 -1.4	GERP -4.3
Regional constraint	o/e 1.01	unconstrained · MANE · 19 kb · p 0.84 · regional, not allelic
Overall
CADD	6.078	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 0.0103% European (non-Finnish) · 122/1,179,738 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00828%

Overall 0.00806% 130/1,613,352 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0103%	9,670
Remaining individualsnot grpmax-eligible	0.00961%	10,410
Admixed American	0.00167%	59,946
African / African-American	0.00134%	74,820

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.Ala112Pro
Coding: c.334G>C
MANE Select: NM_152492
Type: single nucleotide variant
Location: chr1:3754133 (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.Ala112Val Uncertain significance ★ ⚠ same residue
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
CCDC27 p.Arg125Gln 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-ala112pro (accessed [today's date]).

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