Is CCDC110 p.Lys280Arg (c.839A>G) pathogenic?

CCDC110 p.Lys280Arg (c.839A>G) is classified Uncertain significance in CCDC110 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-03). AlphaMissense: likely benign (0.0826); Very rare (popmax 0.00017%, nfe).

How common is CCDC110 p.Lys280Arg (c.839A>G) in the general population?

CCDC110 p.Lys280Arg (c.839A>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CCDC110 p.Lys280Arg (c.839A>G)?

AlphaMissense predicts likely benign (score 0.0826) — an in-silico prediction, not a clinical call.

CCDC110 p.Lys280Arg

c.839A>G · VCV4220290

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0826 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0826	likely benign
REVEL	0.027	moderately benign-leaning
SaProt	LLR -7.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.85	GERP 0.17, phastCons 0.019
Regional constraint	o/e 0.92	unconstrained · MANE · 26 kb · p 0.015 · regional, not allelic
Overall
CADD	2.782	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00017% European (non-Finnish) · 2/1,179,906 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,613,618 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: CCDC110
Protein: p.Lys280Arg
Coding: c.839A>G
MANE Select: NM_152775
Type: single nucleotide variant
Location: chr4:185459748 (GRCh38)
Gene constraint: LOEUF 1.155 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.67

Full CCDC110 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC110 p.Ala207Thr Uncertain significance ★ ⚠ same type
CCDC110 p.Ala654Ser Uncertain significance ★ ⚠ same type
CCDC110 p.Ala68Asp Uncertain significance ★ ⚠ same type
CCDC110 p.Ala816Pro Uncertain significance ★ ⚠ same type
CCDC110 p.Arg202Cys Uncertain significance ★ ⚠ same type
CCDC110 p.Arg566Gln Uncertain significance ★ ⚠ same type
CCDC110 p.Arg566Gly Uncertain significance ★ ⚠ same type
CCDC110 p.Arg660Lys 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/ccdc110-p-lys280arg (accessed [today's date]).

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