Is CCDC166 p.Phe190Leu (c.570C>A) pathogenic?

CCDC166 p.Phe190Leu (c.570C>A) is classified Uncertain significance in CCDC166 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-13). AlphaMissense: likely pathogenic (0.7792); Very rare (popmax 0.00886%, afr).

How common is CCDC166 p.Phe190Leu (c.570C>A) in the general population?

CCDC166 p.Phe190Leu (c.570C>A) is very rare (popmax 0.00886%, afr) (gnomAD).

What do computational predictors say about CCDC166 p.Phe190Leu (c.570C>A)?

AlphaMissense predicts likely pathogenic (score 0.7792) — an in-silico prediction, not a clinical call.

CCDC166 p.Phe190Leu

c.570C>A · rs1458919888 · VCV2244749

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7792 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00886%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7792	likely pathogenic · top 5% in CCDC166
REVEL	0.038	moderately benign-leaning
SaProt	LLR -3.54	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.43	GERP -3, phastCons 0.006
Overall
CADD	8.753	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 0.00886% African / African-American · 6/67,682 alleles

Filtering AF 0.00378% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00259%

Overall 0.000881% 13/1,476,076 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00886%	11,280
European (non-Finnish)	0.000624%	160,173

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.Phe190Leu
Coding: c.570C>A
MANE Select: NM_001162914
dbSNP: rs1458919888
Type: single nucleotide variant
Location: chr8:143707444 (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-phe190leu (accessed [today's date]).

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