Is CEP19 p.Arg95Trp (c.283C>T) pathogenic?

CEP19 p.Arg95Trp (c.283C>T) is classified Uncertain significance in CEP19 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-05-18). Ultra-rare (popmax 0.0103%, nfe); Associated with obesity due to CEP19 deficiency.

What condition is associated with CEP19 p.Arg95Trp (c.283C>T)?

CEP19 p.Arg95Trp (c.283C>T) is associated with obesity due to CEP19 deficiency (ClinVar).

How common is CEP19 p.Arg95Trp (c.283C>T) in the general population?

CEP19 p.Arg95Trp (c.283C>T) is ultra-rare (popmax 0.0103%, nfe) (gnomAD).

CEP19 p.Arg95Trp

c.283C>T · rs201163650 · VCV1384958

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0103%, nfe)

Conditions

obesity due to CEP19 deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.117	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP -2.1, phastCons 0.98
Regional constraint	o/e 1.01	unconstrained · MANE · 1,103 bp · p 0.94 · regional, not allelic
Overall
CADD	19.12	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0103% European (non-Finnish) · 122/1,180,000 alleles

Filtering AF 0.00884% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00828%

Overall 0.0136% 219/1,614,054 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.119%	842
Remaining individualsnot grpmax-eligible	0.0288%	3,472
European (non-Finnish)grpmax	0.0103%	9,672
East Asian	0.00223%	44,886
Admixed American	0.00167%	59,996
South Asian	0.0011%	91,074

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: CEP19
Protein: p.Arg95Trp
Coding: c.283C>T
MANE Select: NM_032898
dbSNP: rs201163650
Type: single nucleotide variant
Location: chr3:196707760 (GRCh38)
Gene constraint: LOEUF 1.208 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.85

Full CEP19 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

obesity due to CEP19 deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CEP19 p.Arg95Gln Uncertain significance ★ same residue
CEP19 p.Arg95Pro Uncertain significance ★ same residue
CEP19 c.-11T>C Benign ★★ same condition
CEP19 p.Arg78Ter Conflicting classifications of pathogenicity ★ same condition
CEP19 p.Arg32His Uncertain significance ★★ same type
CEP19 p.Arg37Ter Uncertain significance ★★ same type
CEP19 p.Asn54Ser Uncertain significance ★★ same type
CEP19 p.Gly27Arg 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/cep19-p-arg95trp (accessed [today's date]).

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