Is CEP85L p.Arg222Trp (c.664C>T) pathogenic?

CEP85L p.Arg222Trp (c.664C>T) is classified Likely benign in CEP85L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-17). AlphaMissense: likely benign (0.0991); Very rare (popmax 0.00441%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEP85L p.Arg222Trp (c.664C>T)?

CEP85L p.Arg222Trp (c.664C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CEP85L p.Arg222Trp (c.664C>T) in the general population?

CEP85L p.Arg222Trp (c.664C>T) is very rare (popmax 0.00441%, nfe) (gnomAD).

What do computational predictors say about CEP85L p.Arg222Trp (c.664C>T)?

AlphaMissense predicts likely benign (score 0.0991) — an in-silico prediction, not a clinical call.

CEP85L p.Arg222Trp

c.664C>T · VCV4001186

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0991 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00441%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0991	likely benign
REVEL	0.261	benign-leaning
SaProt	LLR -8.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 1.7, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 167 kb · p 0.12 · regional, not allelic
Overall
CADD	18.69	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 0.00441% European (non-Finnish) · 52/1,179,986 alleles

Filtering AF 0.00342% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0031%

Overall 0.00669% 108/1,613,982 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0688%	1,453
Remaining individualsnot grpmax-eligible	0.008%	12,501
European (non-Finnish)grpmax	0.00441%	22,692
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,608
African / African-American	0.00267%	37,500
East Asian	0.00223%	44,886
South Asian	0.0022%	45,544
Admixed American	0.00167%	60,010

Finnish 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: CEP85L
Protein: p.Arg222Trp
Coding: c.664C>T
MANE Select: NM_001042475
Type: single nucleotide variant
Location: chr6:118565885 (GRCh38)
Gene constraint: LOEUF 0.696 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.98

Full CEP85L gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP85L p.Arg151Gln Uncertain significance ★★ ⚠ same condition
CEP85L p.Arg241Ser Uncertain significance ★★ ⚠ same condition
CEP85L p.Gly122Ser Uncertain significance ★★ ⚠ same condition
CEP85L p.Ile186Val Uncertain significance ★★ ⚠ same condition
CEP85L p.Pro152Ala Uncertain significance ★★ ⚠ same condition
CEP85L p.Ser262Gly Uncertain significance ★★ ⚠ same condition
CEP85L p.Thr66Ile Uncertain significance ★★ ⚠ same condition
CEP85L p.Lys220Thr Likely benign ★★ same condition

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/cep85l-p-arg222trp (accessed [today's date]).

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