Is CCDC115 p.Arg166Trp (c.496C>T) pathogenic?

CCDC115 p.Arg166Trp (c.496C>T) is classified Uncertain significance in CCDC115 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-29). AlphaMissense: likely benign (0.0878); Ultra-rare (popmax 0.015%, amr); Associated with Inborn genetic diseases.

What condition is associated with CCDC115 p.Arg166Trp (c.496C>T)?

CCDC115 p.Arg166Trp (c.496C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CCDC115 p.Arg166Trp (c.496C>T) in the general population?

CCDC115 p.Arg166Trp (c.496C>T) is ultra-rare (popmax 0.015%, amr) (gnomAD).

What do computational predictors say about CCDC115 p.Arg166Trp (c.496C>T)?

AlphaMissense predicts likely benign (score 0.0878) — an in-silico prediction, not a clinical call.

CCDC115 p.Arg166Trp

c.496C>T · VCV3263787

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0878 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.015%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0878	likely benign
REVEL	0.314	indeterminate
SaProt	LLR -10.10	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 3,002 bp · p 0.28 · regional, not allelic
Overall
CADD	24.0	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 0.015% Admixed American · 9/60,016 alleles

Filtering AF 0.00773% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00578%

Overall 0.00204% 33/1,614,114 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.015%	6,668
Remaining individualsnot grpmax-eligible	0.0144%	6,946
African / African-American	0.00666%	15,005
East Asian	0.00223%	44,884
European (non-Finnish)	0.000763%	131,114

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: CCDC115
Protein: p.Arg166Trp
Coding: c.496C>T
MANE Select: NM_032357
Type: single nucleotide variant
Location: chr2:130339167 (GRCh38)
Gene constraint: LOEUF 1.198 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.32

Full CCDC115 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

VMA22 p.Leu147Pro Uncertain significance ★★ ⚠ same condition
VMA22 p.Met49Lys Uncertain significance ★★ ⚠ same condition
VMA22 p.Ser72Arg Uncertain significance ★★ ⚠ same condition
CCDC115 p.Ala149Thr Uncertain significance ★ ⚠ same condition
CCDC115 p.Arg7Leu Uncertain significance ★ ⚠ same condition
CCDC115 p.Glu93Lys Uncertain significance ★ ⚠ same condition
CCDC115 p.Lys27Asn Uncertain significance ★ ⚠ same condition
CCDC115 p.Tyr47Asn Uncertain significance ★ ⚠ same condition

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/ccdc115-p-arg166trp (accessed [today's date]).

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