Is HEXA p.Phe142fs (c.426del) pathogenic?

HEXA p.Phe142fs (c.426del) is classified Pathogenic in HEXA (ClinVar, Single submitter, 2 submitters; last evaluated 2025-02-18). Ultra-rare (gnomAD MAF 7.142e-07); Associated with Tay-Sachs disease.

What condition is associated with HEXA p.Phe142fs (c.426del)?

HEXA p.Phe142fs (c.426del) is associated with Tay-Sachs disease (ClinVar).

How common is HEXA p.Phe142fs (c.426del) in the general population?

HEXA p.Phe142fs (c.426del) is ultra-rare (gnomAD MAF 7.142e-07) (gnomAD).

How is Tay-Sachs disease inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

HEXA p.Phe142fs

c.426del · rs1057519458 · VCV375350

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

ultra-rare (gnomAD MAF 7.142e-07)

Conditions

Tay-Sachs disease

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 14
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 1.5, phastCons 1

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

Population frequency

dbSNP / gnomAD

Global frequency 7.14e-05% via dbSNP · ultra-rare

No ancestry breakdown or filtering allele frequency is available for this variant, so BA1/BS1 cannot be assessed from this figure alone.

Variant & gene context

Gene: HEXA
Protein: p.Phe142fs
Coding: c.426del
MANE Select: NM_000520
dbSNP: rs1057519458
Type: Deletion
Location: chr15:72353724 (GRCh38)
Gene constraint: LOEUF 0.947 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 93.62 · 2 PDB
Residue 142: an α-helix

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

Disease context

Tay-Sachs disease — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Tay-Sachs disease (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-5 / 10 000 (Specific population)

Similar variants

HEXA c.1525_1526+27del Pathogenic/Likely pathogenic ★★ same condition
HEXA c.237_253+7del Pathogenic ★★ same condition
HEXA p.Ala479fs Pathogenic/Likely pathogenic ★★ same condition
HEXA p.Arg504fs Pathogenic ★★ same condition
HEXA p.Asp395fs Pathogenic/Likely pathogenic ★★ same condition
HEXA p.Gln390fs Pathogenic/Likely pathogenic ★★ same condition
HEXA p.Glu375fs Pathogenic/Likely pathogenic ★★ same condition
HEXA p.Gly250fs Pathogenic/Likely pathogenic ★★ 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/hexa-p-phe142fs (accessed [today's date]).

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