Is CEP85 p.Leu405Phe (c.1215G>T) pathogenic?

CEP85 p.Leu405Phe (c.1215G>T) is classified Benign in CEP85 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-16). AlphaMissense: likely benign (0.1275); Low-frequency (popmax 1.92%, afr).

How common is CEP85 p.Leu405Phe (c.1215G>T) in the general population?

CEP85 p.Leu405Phe (c.1215G>T) is low-frequency (popmax 1.92%, afr) (gnomAD).

What do computational predictors say about CEP85 p.Leu405Phe (c.1215G>T)?

AlphaMissense predicts likely benign (score 0.1275) — an in-silico prediction, not a clinical call.

CEP85 p.Leu405Phe

c.1215G>T · rs75187071 · VCV727178

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1275 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.92%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1275	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -7.20	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 3.1	GERP 1.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 38 kb · p 0.075 · regional, not allelic
Overall
CADD	18.3	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 1.92% African / African-American · 1,441/75,028 alleles

Filtering AF 1.84% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.8%

Overall 0.0989% 1,597/1,614,048 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	1.92%	52
Remaining individualsnot grpmax-eligible	0.122%	822
Admixed American	0.11%	909
Middle Eastern	0.0495%	2,020
South Asian	0.00329%	30,355
European (non-Finnish)	0.000678%	147,494

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: CEP85
Protein: p.Leu405Phe
Coding: c.1215G>T
MANE Select: NM_001319944
dbSNP: rs75187071
Type: single nucleotide variant
Location: chr1:26259676 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.09 · 2 PDB
Residue 405: the 'mediates interaction with nek2 and is required for its function in the suppression of centrosome disjunction' region

Full CEP85 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CEP85 p.Ala176= Benign ★★ same type
CEP85 p.Ala374Pro Uncertain significance ★ ⚠ same type
CEP85 p.Ala396Thr Uncertain significance ★ ⚠ same type
CEP85 p.Ala399Ser Uncertain significance ★ ⚠ same type
CEP85 p.Ala656Val Uncertain significance ★ ⚠ same type
CEP85 p.Arg146Lys Uncertain significance ★ ⚠ same type
CEP85 p.Arg177Lys Uncertain significance ★ ⚠ same type
CEP85 p.Arg237Trp 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/cep85-p-leu405phe (accessed [today's date]).

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