Is LRIG2 p.Arg86Trp (c.256C>T) pathogenic?

LRIG2 p.Arg86Trp (c.256C>T) is classified Uncertain significance in LRIG2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-15). AlphaMissense: ambiguous (0.5429); Very rare (popmax 0.00504%, amr); Associated with urofacial syndrome 2.

What condition is associated with LRIG2 p.Arg86Trp (c.256C>T)?

LRIG2 p.Arg86Trp (c.256C>T) is associated with urofacial syndrome 2 (ClinVar).

How common is LRIG2 p.Arg86Trp (c.256C>T) in the general population?

LRIG2 p.Arg86Trp (c.256C>T) is very rare (popmax 0.00504%, amr) (gnomAD).

What do computational predictors say about LRIG2 p.Arg86Trp (c.256C>T)?

AlphaMissense predicts ambiguous (score 0.5429) — an in-silico prediction, not a clinical call.

LRIG2 p.Arg86Trp

c.256C>T · rs554758747 · VCV548631

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5429 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00504%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

urofacial syndrome 2

Computational evidence

Protein change
AlphaMissense	0.5429	ambiguous
REVEL	0.216	benign-leaning
SaProt	LLR -9.55	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.9	GERP 2.4, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 34 kb · p 0.4 · regional, not allelic
Overall
CADD	26.7	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00504% Admixed American · 3/59,500 alleles

Filtering AF 0.00181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00157%

Overall 0.00206% 33/1,603,834 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00504%	19,833
European (non-Finnish)	0.00256%	39,113

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.Arg86Trp
Coding: c.256C>T
MANE Select: NM_014813
dbSNP: rs554758747
Type: single nucleotide variant
Location: chr1:113091334 (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

urofacial syndrome 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LRIG2 p.Glu11Ter Uncertain significance ★★ same condition
LRIG2 c.2531-22G>A Benign ★★ same condition
LRIG2 p.Thr708= Benign ★★ same condition
LRIG2 c.2530+1G>T Likely pathogenic ★ same condition
LRIG2 c.515+14A>G Uncertain significance ★ same condition
LRIG2 p.His566Tyr Uncertain significance ★ ⚠ same condition
LRIG2 p.Leu848Pro Uncertain significance ★ same condition
LRIG2 p.Arg709Ter 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/lrig2-p-arg86trp (accessed [today's date]).

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