Is CCDC170 p.Arg364Trp (c.1090C>T) pathogenic?

CCDC170 p.Arg364Trp (c.1090C>T) is classified Uncertain significance in CCDC170 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: likely benign (0.1026); Very rare (popmax 0.00133%, afr).

How common is CCDC170 p.Arg364Trp (c.1090C>T) in the general population?

CCDC170 p.Arg364Trp (c.1090C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

What do computational predictors say about CCDC170 p.Arg364Trp (c.1090C>T)?

AlphaMissense predicts likely benign (score 0.1026) — an in-silico prediction, not a clinical call.

CCDC170 p.Arg364Trp

c.1090C>T · VCV3486387

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1026 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1026	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -10.63	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.4	GERP -3.9, phastCons 0.3
Regional constraint	o/e 1.02	unconstrained · MANE · 124 kb · p 0.5 · regional, not allelic
Overall
CADD	20.2	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 0.00133% African / African-American · 1/74,990 alleles

Filtering AF 0.000689% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.00105% 17/1,612,684 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00156%	63,956
African / African-Americangrpmax	0.00133%	74,990
European (non-Finnish)	0.00119%	84,227
South Asian	0.0011%	90,872

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CCDC170
Protein: p.Arg364Trp
Coding: c.1090C>T
MANE Select: NM_025059
Type: single nucleotide variant
Location: chr6:151573489 (GRCh38)
Gene constraint: LOEUF 1.158 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.06
Residue 364: the 'required for binding to microtubules and golgi apparatus location' region

Full CCDC170 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC170 p.Ala17Glu Uncertain significance ★ ⚠ same type
CCDC170 p.Ala17Val Uncertain significance ★ ⚠ same type
CCDC170 p.Ala246Ser Uncertain significance ★ ⚠ same type
CCDC170 p.Ala315Glu Uncertain significance ★ ⚠ same type
CCDC170 p.Ala331Val Uncertain significance ★ ⚠ same type
CCDC170 p.Ala694Asp Uncertain significance ★ ⚠ same type
CCDC170 p.Arg176Cys Uncertain significance ★ ⚠ same type
CCDC170 p.Arg198Gly 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/ccdc170-p-arg364trp (accessed [today's date]).

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