Is CCDC166 p.Pro327Ser (c.979C>T) pathogenic?

CCDC166 p.Pro327Ser (c.979C>T) is classified Likely benign in CCDC166 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-20). AlphaMissense: likely benign (0.0763); Very rare (popmax 0.00227%, nfe).

How common is CCDC166 p.Pro327Ser (c.979C>T) in the general population?

CCDC166 p.Pro327Ser (c.979C>T) is very rare (popmax 0.00227%, nfe) (gnomAD).

What do computational predictors say about CCDC166 p.Pro327Ser (c.979C>T)?

AlphaMissense predicts likely benign (score 0.0763) — an in-silico prediction, not a clinical call.

CCDC166 p.Pro327Ser

c.979C>T · VCV3828305

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0763 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00227%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0763	likely benign
REVEL	0.007	strongly benign-leaning
SaProt	LLR -7.74	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 -3.6	GERP -3.1
Overall
CADD	6.116	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 0.00227% European (non-Finnish) · 26/1,146,556 alleles

Filtering AF 0.00158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00134%

Overall 0.00188% 26/1,383,772 alleles · very rare

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: CCDC166
Protein: p.Pro327Ser
Coding: c.979C>T
MANE Select: NM_001162914
Type: single nucleotide variant
Location: chr8:143707035 (GRCh38)
Gene constraint: LOEUF 1.939 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.10
Residue 327: the 'disordered' region

Full CCDC166 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC166 p.Ala113Asp Uncertain significance ★ ⚠ same type
CCDC166 p.Ala219Val Uncertain significance ★ ⚠ same type
CCDC166 p.Ala222Ser Uncertain significance ★ ⚠ same type
CCDC166 p.Ala31Thr Uncertain significance ★ ⚠ same type
CCDC166 p.Ala39Ser Uncertain significance ★ ⚠ same type
CCDC166 p.Ala430Asp Uncertain significance ★ ⚠ same type
CCDC166 p.Ala434Val Uncertain significance ★ ⚠ same type
CCDC166 p.Arg119Gly 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/ccdc166-p-pro327ser (accessed [today's date]).

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