Is LRIG2 p.Phe187= (c.561C>T) pathogenic?

LRIG2 p.Phe187= (c.561C>T) is classified Likely benign in LRIG2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-03). Ultra-rare (popmax 0.0386%, sas); Associated with LRIG2-related disorder.

What condition is associated with LRIG2 p.Phe187= (c.561C>T)?

LRIG2 p.Phe187= (c.561C>T) is associated with LRIG2-related disorder (ClinVar).

How common is LRIG2 p.Phe187= (c.561C>T) in the general population?

LRIG2 p.Phe187= (c.561C>T) is ultra-rare (popmax 0.0386%, sas) (gnomAD).

LRIG2 p.Phe187=

c.561C>T · rs577814823 · VCV3042713

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0386%, sas)

Conditions

LRIG2-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.71	GERP -3.5, phastCons 0.033
Overall
CADD	9.533	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0386% South Asian · 35/90,574 alleles

Filtering AF 0.0285% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.025%

Overall 0.0026% 42/1,612,820 alleles · ultra-rare exomes 36/1,460,630 · genomes 6/152,190 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0386%	2,588
Remaining individualsnot grpmax-eligible	0.0048%	20,823
East Asian	0.00223%	44,838
European (non-Finnish)	0.000254%	393,174

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.Phe187=
Coding: c.561C>T
MANE Select: NM_014813
dbSNP: rs577814823
Type: single nucleotide variant
Location: chr1:113094384 (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

Disease context

LRIG2-related disorder

Similar variants

LRIG2 c.660-7G>A Likely benign same condition
LRIG2 p.Asp760= Likely benign same condition
LRIG2 p.Asp928= Likely benign same condition
LRIG2 p.Thr765Ile Benign same condition
LRIG2 p.Arg86Trp Uncertain significance ★★ ⚠ same type
LRIG2 p.Glu11Ter Uncertain significance ★★ same type
LRIG2 p.Lys245Arg Uncertain significance ★★ ⚠ same type
LRIG2 c.2531-22G>A Benign ★★ 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-phe187 (accessed [today's date]).

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