Is CFAP20DC p.Arg295Ter (c.883C>T) pathogenic?

CFAP20DC p.Arg295Ter (c.883C>T) is classified Uncertain significance in CFAP20DC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-17). Very rare (popmax 0.00254%, nfe); Associated with tuberous sclerosis 2.

What condition is associated with CFAP20DC p.Arg295Ter (c.883C>T)?

CFAP20DC p.Arg295Ter (c.883C>T) is associated with tuberous sclerosis 2 (ClinVar).

How common is CFAP20DC p.Arg295Ter (c.883C>T) in the general population?

CFAP20DC p.Arg295Ter (c.883C>T) is very rare (popmax 0.00254%, nfe) (gnomAD).

How is Tuberous sclerosis complex inherited?

Typically Autosomal dominant (Orphanet). A genetic counselor can assess individual risk for a family.

CFAP20DC p.Arg295Ter

c.883C>T · VCV3390946

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00254%, nfe)

Conditions

tuberous sclerosis 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 9 of 17
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.41	loss · gain 0.01 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 4.7	GERP 0.89, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00254% European (non-Finnish) · 30/1,178,950 alleles

Filtering AF 0.00181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00157%

Overall 0.00211% 34/1,611,656 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.00321%	31,194
European (non-Finnish)grpmax	0.00254%	39,298
South Asian	0.00221%	45,278

Remaining individuals 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: CFAP20DC
Protein: p.Arg295Ter
Coding: c.883C>T
MANE Select: NM_001394063
Type: single nucleotide variant
Location: chr3:58869460 (GRCh38)
Gene constraint: LOEUF 0.894 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 53.59

Full CFAP20DC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

tuberous sclerosis 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Tuberous sclerosis complex (Orphanet):

Inheritance: Autosomal dominant
Onset: All ages
Prevalence: 1-9 / 100 000 (Taiwan, Province of China)

Similar variants

CFAP20DC p.Arg222His Benign ★★ same type
CFAP20DC p.Gln418Glu Benign/Likely benign ★★ same type
CFAP20DC p.Ile260= Benign ★★ same type
CFAP20DC p.Arg201Ter Uncertain significance ★ same type
CFAP20DC p.Arg362Thr Uncertain significance ★ same type
CFAP20DC p.Cys136Phe Uncertain significance ★ same type
CFAP20DC p.Glu462Gln Uncertain significance ★ same type
CFAP20DC p.His346Pro 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/cfap20dc-p-arg295ter (accessed [today's date]).

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