Is LRIG2 p.Pro696His (c.2087C>A) pathogenic?

LRIG2 p.Pro696His (c.2087C>A) is classified Uncertain significance in LRIG2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2018-09-16). AlphaMissense: likely pathogenic (0.9984); No allele count reported in gnomAD v4.1 (AN 1,569,992).

How common is LRIG2 p.Pro696His (c.2087C>A) in the general population?

LRIG2 p.Pro696His (c.2087C>A) is no allele count reported in gnomAD v4.1 (AN 1,569,992) (gnomAD).

What do computational predictors say about LRIG2 p.Pro696His (c.2087C>A)?

AlphaMissense predicts likely pathogenic (score 0.9984) — an in-silico prediction, not a clinical call.

LRIG2 p.Pro696His

c.2087C>A · rs1557917271 · VCV591358

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9984 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,569,992)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9984	likely pathogenic · top 1% in LRIG2
REVEL	0.898	moderately pathogenic-leaning
SaProt	LLR -16.78	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.7, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 14 kb · p 0.0085 · regional, not allelic
Overall
CADD	28.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

No allele count reported in gnomAD v4.1 (AN 1,569,992). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LRIG2
Protein: p.Pro696His
Coding: c.2087C>A
MANE Select: NM_014813
dbSNP: rs1557917271
Type: single nucleotide variant
Location: chr1:113114433 (GRCh38)
Gene constraint: LOEUF 0.95 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.87
Residue 696: the ig-like c2-type 3 domain

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

Similar variants

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
LRIG2 p.Ala2= Likely benign ★★ same type
LRIG2 p.Asp755Glu Benign ★★ same type
LRIG2 p.Ile155Leu Likely benign ★★ same type
LRIG2 p.Pro882Leu Likely 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-pro696his (accessed [today's date]).

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