Is HLCS p.Ser288fs (c.863del) pathogenic?

HLCS p.Ser288fs (c.863del) is classified Pathogenic/Likely pathogenic in HLCS (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-04-08). No gnomAD frequency available for this variant; Associated with holocarboxylase synthetase deficiency.

What condition is associated with HLCS p.Ser288fs (c.863del)?

HLCS p.Ser288fs (c.863del) is associated with holocarboxylase synthetase deficiency (ClinVar).

How common is HLCS p.Ser288fs (c.863del) in the general population?

HLCS p.Ser288fs (c.863del) is no gnomAD frequency available for this variant (gnomAD).

How is Holocarboxylase synthetase deficiency inherited?

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

HLCS p.Ser288fs

c.863del · rs1015594025 · VCV1453907

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Conditions

holocarboxylase synthetase deficiency

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 11
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -1.4	GERP -4.4

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: HLCS
Protein: p.Ser288fs
Coding: c.863del
MANE Select: NM_001352514
dbSNP: rs1015594025
Type: Deletion
Location: chr21:36937023 (GRCh38)
Gene constraint: LOEUF 0.883 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 77.33

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

Disease context

holocarboxylase synthetase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Holocarboxylase synthetase deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy, Neonatal
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

HLCS c.2114_2121+5del Likely pathogenic ★★ same condition
HLCS p.Arg648fs Likely pathogenic ★★ same condition
HLCS p.Asp544fs Pathogenic/Likely pathogenic ★★ same condition
HLCS p.Gln378fs Pathogenic/Likely pathogenic ★★ same condition
HLCS p.Gln403_Val404insTer Pathogenic/Likely pathogenic ★★ same condition
HLCS p.Gly408fs Pathogenic ★★ same condition
HLCS p.Gly519fs Pathogenic/Likely pathogenic ★★ same condition
HLCS p.His553fs 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/hlcs-p-ser288fs (accessed [today's date]).

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