Is CEP83 p.His63Arg (c.188A>G) pathogenic?

CEP83 p.His63Arg (c.188A>G) is classified Uncertain significance in CEP83 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-28). AlphaMissense: likely benign (0.1193); Very rare (popmax 0.00017%, nfe); Associated with Inborn genetic diseases.

What condition is associated with CEP83 p.His63Arg (c.188A>G)?

CEP83 p.His63Arg (c.188A>G) is associated with Inborn genetic diseases (ClinVar).

How common is CEP83 p.His63Arg (c.188A>G) in the general population?

CEP83 p.His63Arg (c.188A>G) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CEP83 p.His63Arg (c.188A>G)?

AlphaMissense predicts likely benign (score 0.1193) — an in-silico prediction, not a clinical call.

CEP83 p.His63Arg

c.188A>G · VCV3490927

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1193 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1193	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -10.54	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 0.96, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 104 kb · p 0.01 · regional, not allelic
Overall
CADD	18.37	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 0.00017% European (non-Finnish) · 2/1,179,176 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000206% 3/1,458,432 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00157%	63,842
European (non-Finnish)grpmax	0.00017%	589,588

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: CEP83
Protein: p.His63Arg
Coding: c.188A>G
MANE Select: NM_016122
Type: single nucleotide variant
Location: chr12:94411833 (GRCh38)
Gene constraint: LOEUF 0.807 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.90

Full CEP83 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

CEP83 p.Ala243Val Uncertain significance ★★ ⚠ same condition
CEP83 p.Ala248Thr Uncertain significance ★★ ⚠ same condition
CEP83 p.Arg145Ile Uncertain significance ★★ ⚠ same condition
CEP83 p.Arg374Cys Uncertain significance ★★ ⚠ same condition
CEP83 p.Arg448Ser Uncertain significance ★★ ⚠ same condition
CEP83 p.Arg505Lys Uncertain significance ★★ ⚠ same condition
CEP83 p.Arg580Lys Uncertain significance ★★ ⚠ same condition
CEP83 p.Gln425Glu Uncertain significance ★★ ⚠ 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/cep83-p-his63arg (accessed [today's date]).

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