Is HAP1 p.Cys601fs (c.1801_1804delinsCTCCAGAAAGG) pathogenic?

HAP1 p.Cys601fs (c.18011804delinsCTCCAGAAAGG) is classified Uncertain significance in HAP1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-08-07). Associated with HAP1-related disorder.

What condition is associated with HAP1 p.Cys601fs (c.1801_1804delinsCTCCAGAAAGG)?

HAP1 p.Cys601fs (c.1801_1804delinsCTCCAGAAAGG) is associated with HAP1-related disorder (ClinVar).

HAP1 p.Cys601fs

c.1801_1804delinsCTCCAGAAAGG · VCV3347002

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

HAP1-related disorder

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 (11 of 11) — the truncated protein is likely expressed. PVS1 input, not an applied code
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 2.6	GERP -2.4, phastCons 1

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

Variant & gene context

Gene: HAP1
Protein: p.Cys601fs
Coding: c.1801_1804delinsCTCCAGAAAGG
MANE Select: NM_177977
Type: Indel
Location: chr17:41724757 (GRCh38)
Gene constraint: LOEUF 1.31 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.28

Full HAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

HAP1-related disorder

Similar variants

HAP1 p.Ala605fs Uncertain significance ★ same condition
HAP1 p.His569fs Uncertain significance same condition
HAP1 c.1201-4C>T Likely benign same condition
HAP1 c.1201-7C>T Likely benign same condition
HAP1 c.470-7C>G Likely benign same condition
HAP1 c.550-3dup Likely benign same condition
HAP1 p.Ala21= Likely benign same condition
HAP1 p.Ala505Val Benign 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/hap1-p-cys601fs (accessed [today's date]).

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