Is CCDC166 p.Arg207Pro (c.620G>C) pathogenic?

CCDC166 p.Arg207Pro (c.620G>C) is classified Uncertain significance in CCDC166 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-07-20). AlphaMissense: likely pathogenic (0.7991); Rare (popmax 0.251%, afr).

How common is CCDC166 p.Arg207Pro (c.620G>C) in the general population?

CCDC166 p.Arg207Pro (c.620G>C) is rare (popmax 0.251%, afr) (gnomAD).

What do computational predictors say about CCDC166 p.Arg207Pro (c.620G>C)?

AlphaMissense predicts likely pathogenic (score 0.7991) — an in-silico prediction, not a clinical call.

CCDC166 p.Arg207Pro

c.620G>C · rs566385049 · VCV2350024

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7991 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.251%, afr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7991	likely pathogenic · top 4% in CCDC166
REVEL	0.165	moderately benign-leaning
SaProt	LLR -10.26	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP 0.41, phastCons 0.82
Overall
CADD	24.4	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 0.251% African / African-American · 166/66,252 alleles

Filtering AF 0.219% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.207%

Overall 0.0192% 274/1,426,030 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.251%	399
Middle Eastern	0.0754%	1,326
Remaining individualsnot grpmax-eligible	0.0364%	2,748
Admixed American	0.0351%	2,846
European (non-Finnish)	0.00664%	15,050

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.Arg207Pro
Coding: c.620G>C
MANE Select: NM_001162914
dbSNP: rs566385049
Type: single nucleotide variant
Location: chr8:143707394 (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-arg207pro (accessed [today's date]).

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