Is CCDC3 p.Glu33Ala (c.98A>C) pathogenic?

CCDC3 p.Glu33Ala (c.98A>C) is classified Uncertain significance in CCDC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-30). AlphaMissense: likely pathogenic (0.6079); Ultra-rare (popmax 0.0152%, amr).

How common is CCDC3 p.Glu33Ala (c.98A>C) in the general population?

CCDC3 p.Glu33Ala (c.98A>C) is ultra-rare (popmax 0.0152%, amr) (gnomAD).

What do computational predictors say about CCDC3 p.Glu33Ala (c.98A>C)?

AlphaMissense predicts likely pathogenic (score 0.6079) — an in-silico prediction, not a clinical call.

CCDC3 p.Glu33Ala

c.98A>C · rs1169425720 · VCV2396005

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6079 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0152%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6079	likely pathogenic
REVEL	0.21	benign-leaning
SaProt	LLR -4.05	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 3.2, phastCons 1
Regional constraint	o/e 1.18	unconstrained · MANE · 103 kb · p 0.00074 · regional, not allelic
Overall
CADD	26.4	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 0.0152% Admixed American · 5/32,876 alleles

Filtering AF 0.00594% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.000352% 5/1,419,340 alleles · ultra-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: CCDC3
Protein: p.Glu33Ala
Coding: c.98A>C
MANE Select: NM_031455
dbSNP: rs1169425720
Type: single nucleotide variant
Location: chr10:13001473 (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-glu33ala (accessed [today's date]).

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