Is CCDC28B p.Phe110= (c.330C>T) pathogenic?

CCDC28B p.Phe110= (c.330C>T) is classified Uncertain significance in CCDC28B (ClinVar, Single submitter, 3 submitters; last evaluated 2023-04-19). Common (popmax 6.41%, mid) — too common for a highly-penetrant pathogenic allele; Associated with CCDC28B-related disorder.

What condition is associated with CCDC28B p.Phe110= (c.330C>T)?

CCDC28B p.Phe110= (c.330C>T) is associated with CCDC28B-related disorder, Bardet-Biedl syndrome (ClinVar).

CCDC28B p.Phe110=

Q: How common is CCDC28B p.Phe110= (c.330C>T) in the general population?

CCDC28B p.Phe110= (c.330C>T) is common (popmax 6.41%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.330C>T · rs41263993 · VCV1326

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 6.41%, mid) — too common for a highly-penetrant pathogenic allele

Conditions

CCDC28B-related disorder

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 -11	GERP -4.8
Overall
CADD	4.578	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 6.41% Middle Eastern · 369/5,760 alleles

Filtering AF 5.87% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.66%

Overall 1.28% 19,949/1,554,330 alleles · common exomes 18,358/1,402,106 · genomes 1,591/152,224 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	6.72%	15
Middle Easterngrpmax	6.41%	16
Remaining individualsnot grpmax-eligible	1.72%	58
European (non-Finnish)	1.31%	76
Admixed American	1.08%	93
South Asian	1.06%	94
African / African-American	0.358%	279
Amishnot grpmax-eligible	0.219%	456
Finnishnot grpmax-eligible	0.113%	884
East Asian	0.00226%	44,194

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: CCDC28B
Protein: p.Phe110=
Coding: c.330C>T
MANE Select: NM_024296
dbSNP: rs41263993
Type: single nucleotide variant
Location: chr1:32204044 (GRCh38)
Gene constraint: LOEUF 1.357 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.15

Full CCDC28B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

CCDC28B-related disorder

Also linked: Bardet-Biedl syndrome

Similar variants

CCDC28B c.549-8G>C Likely benign same condition
CCDC28B p.Lys112= Uncertain significance ★★ same type
CCDC28B p.Arg25Trp Benign ★★ same type
CCDC28B p.Glu154= Benign/Likely benign ★★ same type
CCDC28B p.Gly155Arg Benign/Likely benign ★★ same type
CCDC28B p.Ala199Asp Uncertain significance ★ ⚠ same type
CCDC28B p.Ala20Val Uncertain significance ★ ⚠ same type
CCDC28B p.Ala73Pro 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/ccdc28b-p-phe110 (accessed [today's date]).

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