Is CCDC33 p.Arg555Trp (c.1663C>T) pathogenic?

CCDC33 p.Arg555Trp (c.1663C>T) is classified Uncertain significance in CCDC33 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-10). Very rare (popmax 0.0033%, sas).

How common is CCDC33 p.Arg555Trp (c.1663C>T) in the general population?

CCDC33 p.Arg555Trp (c.1663C>T) is very rare (popmax 0.0033%, sas) (gnomAD).

CCDC33 p.Arg555Trp

c.1663C>T · rs368665468 · VCV2218892

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0033%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.16	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -3.3
Regional constraint	o/e 1.00	unconstrained · MANE · 99 kb · p 0.88 · regional, not allelic
Overall
CADD	20.5	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0033% South Asian · 3/90,844 alleles

Filtering AF 0.000954% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.00242% 39/1,612,792 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0441%	2,268
Remaining individualsnot grpmax-eligible	0.00641%	15,608
South Asiangrpmax	0.0033%	30,281
European (non-Finnish)	0.00153%	65,521
African / African-American	0.00133%	74,914

Ashkenazi Jewish 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: CCDC33
Protein: p.Arg555Trp
Coding: c.1663C>T
MANE Select: NM_025055
dbSNP: rs368665468
Type: single nucleotide variant
Location: chr15:74331098 (GRCh38)
Gene constraint: LOEUF 1.17 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.34

Full CCDC33 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC33 p.Pro610Leu Likely benign ★★ same type
STRA6 c.96+1744C>G Benign ★★ same type
STRA6 c.-15-751T>G Benign ★★ same type
STRA6 c.-16+1061C>G Likely benign ★★ same type
STRA6 c.-16+1161G>A Benign ★★ same type
STRA6 c.-16+794G>C Benign ★★ same type
STRA6 c.-5200G>A Benign ★★ same type
STRA6 p.Trp15Ter Likely pathogenic ★ 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/ccdc33-p-arg555trp (accessed [today's date]).

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