Is LRIG2 p.Phe331fs (c.993del) pathogenic?

LRIG2 p.Phe331fs (c.993del) is classified Uncertain significance in LRIG2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-09-16). Very rare (popmax 0.00133%, afr).

How common is LRIG2 p.Phe331fs (c.993del) in the general population?

LRIG2 p.Phe331fs (c.993del) is very rare (popmax 0.00133%, afr) (gnomAD).

LRIG2 p.Phe331fs

c.993del · rs1326615116 · VCV591212

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

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 18
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.4	GERP -0.058, phastCons 0.99
Overall
CADD	33.0	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

Grpmax group 0.00133% African / African-American · 1/74,920 alleles

Overall 6.2e-05% 1/1,614,012 alleles · very rare exomes 0/1,461,852 · genomes 1/152,160 · 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: LRIG2
Protein: p.Phe331fs
Coding: c.993del
MANE Select: NM_014813
dbSNP: rs1326615116
Type: Deletion
Location: chr1:113096265 (GRCh38)
Gene constraint: LOEUF 0.95 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.87

Full LRIG2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LRIG2 p.Phe331Leu Uncertain significance ★ ⚠ same residue
LRIG2 p.Glu926fs Likely pathogenic ★ same type
LRIG2 p.Leu6fs Pathogenic ★ same type
LRIG2 p.Ser175fs Likely pathogenic ★ same type
LRIG2 p.Thr363_Leu364insTer Likely pathogenic ★ same type
LRIG2 p.Arg224fs Uncertain significance ★ same type
LRIG2 p.Glu410fs Pathogenic same type
LRIG2 p.Ser697fs Pathogenic same type

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/lrig2-p-phe331fs (accessed [today's date]).

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