Is MLPH p.Glu98Ter (c.292G>T) pathogenic?

MLPH p.Glu98Ter (c.292G>T) is classified Pathogenic in MLPH (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-05-23). Absent from gnomAD v4.1; Associated with Griscelli syndrome type 3.

What condition is associated with MLPH p.Glu98Ter (c.292G>T)?

MLPH p.Glu98Ter (c.292G>T) is associated with Griscelli syndrome type 3 (ClinVar).

How common is MLPH p.Glu98Ter (c.292G>T) in the general population?

MLPH p.Glu98Ter (c.292G>T) is absent from gnomAD v4.1 (gnomAD).

How is Griscelli syndrome inherited?

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

MLPH p.Glu98Ter

c.292G>T · rs146551411 · VCV1686914

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

Griscelli syndrome type 3

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 16
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP 0.85, phastCons 0.98
Overall
CADD	35.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MLPH
Protein: p.Glu98Ter
Coding: c.292G>T
MANE Select: NM_024101
dbSNP: rs146551411
Type: single nucleotide variant
Location: chr2:237510755 (GRCh38)
Gene constraint: LOEUF 0.856 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 61.58
Residue 98: the rabbd domain

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.Glu98Lys Conflicting classifications of pathogenicity ★ ⚠ same residue
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
MLPH c.332+1G>T 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/mlph-p-glu98ter (accessed [today's date]).

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