Is LRIG2 p.Gln952Pro (c.2855A>C) pathogenic?

LRIG2 p.Gln952Pro (c.2855A>C) is classified Uncertain significance in LRIG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-19). AlphaMissense: likely benign (0.1183); Ultra-rare (popmax 0.0165%, mid).

How common is LRIG2 p.Gln952Pro (c.2855A>C) in the general population?

LRIG2 p.Gln952Pro (c.2855A>C) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about LRIG2 p.Gln952Pro (c.2855A>C)?

AlphaMissense predicts likely benign (score 0.1183) — an in-silico prediction, not a clinical call.

LRIG2 p.Gln952Pro

c.2855A>C · rs1210989908 · VCV2337158

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1183 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1183	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -5.45	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.47, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 14 kb · p 0.0085 · regional, not allelic
Overall
CADD	13.85	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.0165% Middle Eastern · 1/6,062 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,614,118 alleles · ultra-rare exomes 4/1,461,890 · genomes 0/152,228 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,062
Remaining individualsnot grpmax-eligible	0.0016%	62,510
European (non-Finnish)	0.000169%	590,016

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.Gln952Pro
Coding: c.2855A>C
MANE Select: NM_014813
dbSNP: rs1210989908
Type: single nucleotide variant
Location: chr1:113119407 (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.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-gln952pro (accessed [today's date]).

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