Is CCDC166 p.Pro279Leu (c.836C>T) pathogenic?

CCDC166 p.Pro279Leu (c.836C>T) is classified Uncertain significance in CCDC166 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely benign (0.184); Very rare (popmax 0.00154%, afr).

How common is CCDC166 p.Pro279Leu (c.836C>T) in the general population?

CCDC166 p.Pro279Leu (c.836C>T) is very rare (popmax 0.00154%, afr) (gnomAD).

What do computational predictors say about CCDC166 p.Pro279Leu (c.836C>T)?

AlphaMissense predicts likely benign (score 0.184) — an in-silico prediction, not a clinical call.

CCDC166 p.Pro279Leu

c.836C>T · VCV3486223

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.184 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00154%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.184	likely benign
REVEL	0.232	benign-leaning
SaProt	LLR -6.46	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 8.8	GERP 1.4, phastCons 1
Overall
CADD	24.4	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 0.00154% African / African-American · 1/65,116 alleles

Overall 0.000162% 2/1,235,698 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00154%	65,116
European (non-Finnish)	9.26e-05%	1,080,432

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.Pro279Leu
Coding: c.836C>T
MANE Select: NM_001162914
Type: single nucleotide variant
Location: chr8:143707178 (GRCh38)
Gene constraint: LOEUF 1.939 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.10
Residue 279: 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-pro279leu (accessed [today's date]).

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