Is LNPK p.Phe296= (c.888T>C) pathogenic?

LNPK p.Phe296= (c.888T>C) is classified Likely benign in LNPK (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-10-01). Ultra-rare (popmax 0.038%, eas); Associated with LNPK-related disorder.

What condition is associated with LNPK p.Phe296= (c.888T>C)?

LNPK p.Phe296= (c.888T>C) is associated with LNPK-related disorder (ClinVar).

How common is LNPK p.Phe296= (c.888T>C) in the general population?

LNPK p.Phe296= (c.888T>C) is ultra-rare (popmax 0.038%, eas) (gnomAD).

LNPK p.Phe296=

c.888T>C · rs554332202 · VCV3032918

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.038%, eas)

Conditions

LNPK-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>T here scores Δ0.27 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.1	GERP -1.3, phastCons 1
Overall
CADD	7.392	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.038% East Asian · 17/44,766 alleles

Filtering AF 0.0241% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0198%

Overall 0.00106% 17/1,607,488 alleles · ultra-rare exomes 11/1,455,200 · genomes 6/152,288 · 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: LNPK
Protein: p.Phe296=
Coding: c.888T>C
MANE Select: NM_030650
dbSNP: rs554332202
Type: single nucleotide variant
Location: chr2:175937510 (GRCh38)
Gene constraint: LOEUF 0.964 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.98
Residue 296: a UniProt-annotated variant site (in nedehcc)

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

Disease context

LNPK-related disorder

Similar variants

LNPK p.Ser143Ter Likely pathogenic ★ same condition
LNPK p.Gln269Arg Uncertain significance ★ same condition
LNPK c.258-7C>T Likely benign same condition
LNPK c.70-10C>G Benign same condition
LNPK c.707-1347A>G Benign same condition
LNPK c.-18A>G Likely benign same condition
LNPK p.Thr159Ser Benign same condition
LNPK c.707-1428dup Likely 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/lnpk-p-phe296 (accessed [today's date]).

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