Is CCDC8 p.Arg485= (c.1455C>G) pathogenic?

CCDC8 p.Arg485= (c.1455C>G) is classified Benign/Likely benign in CCDC8 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-14). Very rare (popmax 0.004%, afr).

How common is CCDC8 p.Arg485= (c.1455C>G) in the general population?

CCDC8 p.Arg485= (c.1455C>G) is very rare (popmax 0.004%, afr) (gnomAD).

CCDC8 p.Arg485=

c.1455C>G · rs200336737 · VCV1600931

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.004%, 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 -0.089	GERP -2.4, phastCons 0.36
Overall
CADD	7.221	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,934 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00186% 30/1,614,072 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,978
European (non-Finnish)	0.00212%	47,201
Remaining individualsnot grpmax-eligible	0.0016%	62,490
South Asian	0.0011%	91,088

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.Arg485=
Coding: c.1455C>G
MANE Select: NM_032040
dbSNP: rs200336737
Type: single nucleotide variant
Location: chr19:46411356 (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.Arg485His Uncertain significance ★★ ⚠ same residue
CCDC8 p.Arg485Pro Uncertain significance ★★ ⚠ same residue
CCDC8 p.Arg485Cys Uncertain significance ★ ⚠ same residue
CCDC8 p.Arg485Gly 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

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-arg485 (accessed [today's date]).

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