Is CCDC8 p.Pro14= (c.42C>T) pathogenic?

CCDC8 p.Pro14= (c.42C>T) is classified Likely benign in CCDC8 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-21). Ultra-rare (popmax 0.068%, afr).

How common is CCDC8 p.Pro14= (c.42C>T) in the general population?

CCDC8 p.Pro14= (c.42C>T) is ultra-rare (popmax 0.068%, afr) (gnomAD).

CCDC8 p.Pro14=

c.42C>T · rs149339215 · VCV1345633

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.068%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.41	GERP -2.7, phastCons 0.022
Overall
CADD	7.398	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.068% African / African-American · 51/75,018 alleles

Filtering AF 0.0531% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0478%

Overall 0.00341% 55/1,614,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.068%	1,471
Remaining individualsnot grpmax-eligible	0.0064%	15,628

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.Pro14=
Coding: c.42C>T
MANE Select: NM_032040
dbSNP: rs149339215
Type: single nucleotide variant
Location: chr19:46412769 (GRCh38)
Gene constraint: LOEUF 1.796 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 46.83 · 1 PDB

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

Similar variants

CCDC8 p.Pro14Leu Uncertain significance ★ ⚠ same residue
CCDC8 p.Pro14Thr Uncertain significance ★ ⚠ same residue
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

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-pro14 (accessed [today's date]).

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