Is CEP85L p.Arg380Trp (c.1138C>T) pathogenic?

CEP85L p.Arg380Trp (c.1138C>T) is classified Likely benign in CEP85L (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: ambiguous (0.5515); Ultra-rare (popmax 0.0329%, amr); Associated with Inborn genetic diseases.

What condition is associated with CEP85L p.Arg380Trp (c.1138C>T)?

CEP85L p.Arg380Trp (c.1138C>T) is associated with Inborn genetic diseases (ClinVar).

How common is CEP85L p.Arg380Trp (c.1138C>T) in the general population?

CEP85L p.Arg380Trp (c.1138C>T) is ultra-rare (popmax 0.0329%, amr) (gnomAD).

What do computational predictors say about CEP85L p.Arg380Trp (c.1138C>T)?

AlphaMissense predicts ambiguous (score 0.5515) — an in-silico prediction, not a clinical call.

CEP85L p.Arg380Trp

c.1138C>T · VCV4613964

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5515 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5515	ambiguous
REVEL	0.198	benign-leaning
SaProt	LLR -9.94	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 5.9	GERP 1.1, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 167 kb · p 0.12 · 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 0.0329% Admixed American · 19/57,776 alleles

Filtering AF 0.0215% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0179%

Overall 0.00318% 45/1,414,776 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0329%	3,041
European (non-Finnish)	0.00249%	40,168
East Asian	0.00229%	43,682

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.Arg380Trp
Coding: c.1138C>T
MANE Select: NM_001042475
Type: single nucleotide variant
Location: chr6:118523803 (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-arg380trp (accessed [today's date]).

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