Is CCDC3 p.Pro266Arg (c.797C>G) pathogenic?

CCDC3 p.Pro266Arg (c.797C>G) is classified Uncertain significance in CCDC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-25). AlphaMissense: likely benign (0.069); Ultra-rare (popmax 0.0188%, afr).

How common is CCDC3 p.Pro266Arg (c.797C>G) in the general population?

CCDC3 p.Pro266Arg (c.797C>G) is ultra-rare (popmax 0.0188%, afr) (gnomAD).

What do computational predictors say about CCDC3 p.Pro266Arg (c.797C>G)?

AlphaMissense predicts likely benign (score 0.069) — an in-silico prediction, not a clinical call.

CCDC3 p.Pro266Arg

c.797C>G · rs116856516 · VCV2519121

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.069 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0188%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.069	likely benign
REVEL	0.053	moderately benign-leaning
SaProt	LLR -5.99	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 3.2	GERP 0.35, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 103 kb · p 0.00074 · regional, not allelic
Overall
CADD	17.76	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 0.0188% African / African-American · 14/74,474 alleles

Filtering AF 0.0113% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0091%

Overall 0.00848% 136/1,603,304 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0188%	5,320
Ashkenazi Jewishnot grpmax-eligible	0.017%	5,874
East Asian	0.0134%	7,442
Remaining individualsnot grpmax-eligible	0.0113%	8,841
South Asian	0.011%	9,066
European (non-Finnish)	0.00767%	13,039
Admixed American	0.00674%	14,828

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: CCDC3
Protein: p.Pro266Arg
Coding: c.797C>G
MANE Select: NM_031455
dbSNP: rs116856516
Type: single nucleotide variant
Location: chr10:12898432 (GRCh38)
Gene constraint: LOEUF 1.79 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.13

Full CCDC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC3 p.Ala19Val Uncertain significance ★ ⚠ same type
CCDC3 p.Ala21Ser Uncertain significance ★ ⚠ same type
CCDC3 p.Ala21Thr Uncertain significance ★ ⚠ same type
CCDC3 p.Ala250Val Uncertain significance ★ ⚠ same type
CCDC3 p.Ala253Thr Uncertain significance ★ ⚠ same type
CCDC3 p.Arg20Cys Uncertain significance ★ ⚠ same type
CCDC3 p.Arg213Cys Uncertain significance ★ ⚠ same type
CCDC3 p.Arg215Trp 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/ccdc3-p-pro266arg (accessed [today's date]).

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