Is CCDC166 p.Arg36Ser (c.106C>A) pathogenic?

CCDC166 p.Arg36Ser (c.106C>A) is classified Uncertain significance in CCDC166 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). AlphaMissense: ambiguous (0.5034); Very rare (popmax 8.78e-05%, nfe).

How common is CCDC166 p.Arg36Ser (c.106C>A) in the general population?

CCDC166 p.Arg36Ser (c.106C>A) is very rare (popmax 8.78e-05%, nfe) (gnomAD).

What do computational predictors say about CCDC166 p.Arg36Ser (c.106C>A)?

AlphaMissense predicts ambiguous (score 0.5034) — an in-silico prediction, not a clinical call.

CCDC166 p.Arg36Ser

c.106C>A · VCV3263988

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5034 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.78e-05%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5034	ambiguous
REVEL	0.175	moderately benign-leaning
SaProt	LLR -8.29	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.8, phastCons 1
Overall
CADD	21.0	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 8.78e-05% European (non-Finnish) · 1/1,139,464 alleles

Overall 7.28e-05% 1/1,374,002 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.Arg36Ser
Coding: c.106C>A
MANE Select: NM_001162914
Type: single nucleotide variant
Location: chr8:143708004 (GRCh38)
Gene constraint: LOEUF 1.939 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.10

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-arg36ser (accessed [today's date]).

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