Is CCDC110 p.Ala816Pro (c.2446G>C) pathogenic?

CCDC110 p.Ala816Pro (c.2446G>C) is classified Uncertain significance in CCDC110 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-16). AlphaMissense: likely benign (0.0903); Rare (popmax 0.265%, afr).

How common is CCDC110 p.Ala816Pro (c.2446G>C) in the general population?

CCDC110 p.Ala816Pro (c.2446G>C) is rare (popmax 0.265%, afr) (gnomAD).

What do computational predictors say about CCDC110 p.Ala816Pro (c.2446G>C)?

AlphaMissense predicts likely benign (score 0.0903) — an in-silico prediction, not a clinical call.

CCDC110 p.Ala816Pro

c.2446G>C · VCV3828057

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0903 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.265%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0903	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -5.53	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 1	GERP -0.64, phastCons 0.47
Regional constraint	o/e 0.92	unconstrained · MANE · 26 kb · p 0.015 · regional, not allelic
Overall
CADD	12.23	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 0.265% African / African-American · 190/71,746 alleles

Filtering AF 0.234% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.222%

Overall 0.0138% 215/1,553,702 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.265%	378
Admixed American	0.0363%	2,756
Remaining individualsnot grpmax-eligible	0.0151%	6,632

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.Ala816Pro
Coding: c.2446G>C
MANE Select: NM_152775
Type: single nucleotide variant
Location: chr4:185458141 (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.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
CCDC110 p.Arg765Gln 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-ala816pro (accessed [today's date]).

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