Is CEP68 p.Arg669Trp (c.2005C>T) pathogenic?

CEP68 p.Arg669Trp (c.2005C>T) is classified Uncertain significance in CEP68 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-28). AlphaMissense: ambiguous (0.5101); Ultra-rare (popmax 0.0156%, eas).

How common is CEP68 p.Arg669Trp (c.2005C>T) in the general population?

CEP68 p.Arg669Trp (c.2005C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about CEP68 p.Arg669Trp (c.2005C>T)?

AlphaMissense predicts ambiguous (score 0.5101) — an in-silico prediction, not a clinical call.

CEP68 p.Arg669Trp

c.2005C>T · VCV4001110

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5101 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5101	ambiguous · top 10% in CEP68
REVEL	0.279	benign-leaning
SaProt	LLR -8.26	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 1.4, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 13 kb · p 0.74 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,896 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.00428% 69/1,613,956 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,414
Finnishnot grpmax-eligible	0.00781%	12,803
Remaining individualsnot grpmax-eligible	0.0048%	20,828
European (non-Finnish)	0.00424%	23,600
African / African-American	0.00267%	37,451
Admixed American	0.00167%	60,004
South Asian	0.0011%	91,076

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: CEP68
Protein: p.Arg669Trp
Coding: c.2005C>T
MANE Select: NM_015147
Type: single nucleotide variant
Location: chr2:65074402 (GRCh38)
Gene constraint: LOEUF 0.627 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 49.36

Full CEP68 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP68 p.Arg669Gln Uncertain significance ★ ⚠ same residue
CEP68 c.2007+9C>G Benign ★★ same type
CEP68 p.Arg217His Benign ★★ ⚠ same type
CEP68 p.His566= Benign/Likely benign ★★ same type
CEP68 p.Phe367Tyr Benign ★★ same type
CEP68 p.Ser447= Benign ★★ same type
CEP68 p.Val607Ala Benign ★★ same type
CEP68 p.Ala163Thr 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/cep68-p-arg669trp (accessed [today's date]).

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