Is CCDC8 p.Glu337Ala (c.1010A>C) pathogenic?

CCDC8 p.Glu337Ala (c.1010A>C) is classified Likely benign in CCDC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-18). AlphaMissense: likely benign (0.0796); Very rare (popmax 6.87e-05%); Associated with Inborn genetic diseases.

What condition is associated with CCDC8 p.Glu337Ala (c.1010A>C)?

CCDC8 p.Glu337Ala (c.1010A>C) is associated with Inborn genetic diseases (ClinVar).

How common is CCDC8 p.Glu337Ala (c.1010A>C) in the general population?

CCDC8 p.Glu337Ala (c.1010A>C) is very rare (popmax 6.87e-05%) (gnomAD).

What do computational predictors say about CCDC8 p.Glu337Ala (c.1010A>C)?

AlphaMissense predicts likely benign (score 0.0796) — an in-silico prediction, not a clinical call.

CCDC8 p.Glu337Ala

c.1010A>C · VCV4606973

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0796 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 6.87e-05%)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0796	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -8.17	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 -5	GERP -2.6
Regional constraint	o/e 1.02	unconstrained · MANE · 1,613 bp · p 0.66 · regional, not allelic
Overall
CADD	1.188	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 6.87e-05%

Overall 6.87e-05% 1/1,455,410 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: CCDC8
Protein: p.Glu337Ala
Coding: c.1010A>C
MANE Select: NM_032040
Type: single nucleotide variant
Location: chr19:46411801 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 46.83 · 1 PDB
Residue 337: the 'disordered' region

Full CCDC8 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

CCDC8 p.Ala217Thr Uncertain significance ★★ ⚠ same condition
CCDC8 p.Ala293Thr Uncertain significance ★★ ⚠ same condition
CCDC8 p.Ala393Val Uncertain significance ★★ ⚠ same condition
CCDC8 p.Ala527Val Uncertain significance ★★ ⚠ same condition
CCDC8 p.Arg15Gln Uncertain significance ★★ ⚠ same condition
CCDC8 p.Arg225Gly Uncertain significance ★★ ⚠ same condition
CCDC8 p.Arg277His Uncertain significance ★★ ⚠ same condition
CCDC8 p.Arg277Ser 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/ccdc8-p-glu337ala (accessed [today's date]).

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