Is CCDC8 p.Asp357= (c.1071T>C) pathogenic?

CCDC8 p.Asp357= (c.1071T>C) is classified Likely benign in CCDC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-08). Very rare (popmax 0.000932%, nfe).

How common is CCDC8 p.Asp357= (c.1071T>C) in the general population?

CCDC8 p.Asp357= (c.1071T>C) is very rare (popmax 0.000932%, nfe) (gnomAD).

CCDC8 p.Asp357=

c.1071T>C · VCV4697746

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000932%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.014	strongly benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -0.79
Overall
CADD	3.415	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000932% European (non-Finnish) · 11/1,179,762 alleles

Filtering AF 0.0005% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.00385% 62/1,612,472 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0751%	1,331
Remaining individualsnot grpmax-eligible	0.0048%	20,815
European (non-Finnish)grpmax	0.000932%	107,251

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Asp357=
Coding: c.1071T>C
MANE Select: NM_032040
Type: single nucleotide variant
Location: chr19:46411740 (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 357: the 'disordered' region

Full CCDC8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC8 p.Ala217Thr Uncertain significance ★★ ⚠ same type
CCDC8 p.Ala293Thr Uncertain significance ★★ ⚠ same type
CCDC8 p.Ala393Val Uncertain significance ★★ ⚠ same type
CCDC8 p.Ala527Val Uncertain significance ★★ ⚠ same type
CCDC8 p.Arg15Gln Uncertain significance ★★ ⚠ same type
CCDC8 p.Arg225Gly Uncertain significance ★★ ⚠ same type
CCDC8 p.Arg277His Uncertain significance ★★ ⚠ same type
CCDC8 p.Arg277Ser 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/ccdc8-p-asp357 (accessed [today's date]).

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