Is CEP85 p.Arg359Gln (c.1076G>A) pathogenic?

CEP85 p.Arg359Gln (c.1076G>A) is classified Uncertain significance in CEP85 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-27). AlphaMissense: likely benign (0.1573); Very rare (popmax 0.00119%, nfe).

How common is CEP85 p.Arg359Gln (c.1076G>A) in the general population?

CEP85 p.Arg359Gln (c.1076G>A) is very rare (popmax 0.00119%, nfe) (gnomAD).

What do computational predictors say about CEP85 p.Arg359Gln (c.1076G>A)?

AlphaMissense predicts likely benign (score 0.1573) — an in-silico prediction, not a clinical call.

CEP85 p.Arg359Gln

c.1076G>A · rs752417892 · VCV2292008

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1573 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1573	likely benign
REVEL	0.657	pathogenic-leaning
SaProt	LLR -6.74	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	GERP 1.9, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 38 kb · p 0.075 · regional, not allelic
Overall
CADD	32.0	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 0.00119% European (non-Finnish) · 14/1,180,016 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000929% 15/1,614,000 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00119%	84,287
South Asian	0.0011%	91,066

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.Arg359Gln
Coding: c.1076G>A
MANE Select: NM_001319944
dbSNP: rs752417892
Type: single nucleotide variant
Location: chr1:26258181 (GRCh38)
Gene constraint: LOEUF 0.784 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.09 · 2 PDB
Residue 359: 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.Leu405Phe 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

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-arg359gln (accessed [today's date]).

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