Is MLPH p.Lys330fs (c.987del) pathogenic?

MLPH p.Lys330fs (c.987del) is classified Pathogenic in MLPH (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-25). Very rare (popmax 8.47e-05%, nfe); Associated with Griscelli syndrome type 3.

What condition is associated with MLPH p.Lys330fs (c.987del)?

MLPH p.Lys330fs (c.987del) is associated with Griscelli syndrome type 3 (ClinVar).

How common is MLPH p.Lys330fs (c.987del) in the general population?

MLPH p.Lys330fs (c.987del) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

How is Griscelli syndrome inherited?

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

MLPH p.Lys330fs

c.987del · rs786205641 · VCV191315

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Conditions

Griscelli syndrome type 3

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 8 of 16
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.62	GERP -4.2

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,180,030 alleles

Overall 6.2e-05% 1/1,614,134 alleles · very rare exomes 1/1,461,892 · genomes 0/152,242 · joint denominator

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: MLPH
Protein: p.Lys330fs
Coding: c.987del
MANE Select: NM_024101
dbSNP: rs786205641
Type: Deletion
Location: chr2:237527482 (GRCh38)
Gene constraint: LOEUF 0.856 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 61.58

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

Disease context

Griscelli syndrome type 3 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Griscelli syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Childhood, Infancy

Similar variants

MLPH p.Ala321_His322insTer Likely pathogenic ★ same condition
MLPH p.Asp379fs Uncertain significance ★ same condition
MLPH p.Arg35Gln Pathogenic/Likely pathogenic ★★ same condition
MLPH p.Arg35Trp Pathogenic/Likely pathogenic ★★ same condition
MLPH p.Arg518Gly Uncertain significance ★★ ⚠ same condition
MLPH p.Glu174= Benign/Likely benign ★★ same condition
MLPH p.Glu407= Benign ★★ same condition
MLPH p.Val374Ala 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/mlph-p-lys330fs (accessed [today's date]).

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