Is CEP19 p.His58fs (c.170dup) pathogenic?

CEP19 p.His58fs (c.170dup) is classified Uncertain significance in CEP19 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-16). Very rare (popmax 0.00167%, amr).

How common is CEP19 p.His58fs (c.170dup) in the general population?

CEP19 p.His58fs (c.170dup) is very rare (popmax 0.00167%, amr) (gnomAD).

CEP19 p.His58fs

c.170dup · rs2108662934 · VCV1473039

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	escapes	premature termination codon in the last exon (3 of 3) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.12	GERP -2.7, phastCons 0.74

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,016 alleles

Overall 6.84e-05% 1/1,460,966 alleles · very rare

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.His58fs
Coding: c.170dup
MANE Select: NM_032898
dbSNP: rs2108662934
Type: Duplication
Location: chr3:196707872 (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

Similar variants

CEP19 p.His58Tyr Uncertain significance ★ same residue
CEP19 p.His58= Likely benign ★ same residue
CEP19 p.Tyr61Ter Pathogenic 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-his58fs (accessed [today's date]).

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