Is LRIG2 p.Ile439Phe (c.1315A>T) pathogenic?

LRIG2 p.Ile439Phe (c.1315A>T) is classified Uncertain significance in LRIG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-10-03). AlphaMissense: likely benign (0.1592); Ultra-rare (popmax 0.0549%, afr).

How common is LRIG2 p.Ile439Phe (c.1315A>T) in the general population?

LRIG2 p.Ile439Phe (c.1315A>T) is ultra-rare (popmax 0.0549%, afr) (gnomAD).

What do computational predictors say about LRIG2 p.Ile439Phe (c.1315A>T)?

AlphaMissense predicts likely benign (score 0.1592) — an in-silico prediction, not a clinical call.

LRIG2 p.Ile439Phe

c.1315A>T · rs568784194 · VCV2376318

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1592 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0549%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1592	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -4.91	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 2.6	GERP -3.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 34 kb · p 0.4 · regional, not allelic
Overall
CADD	14.69	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 0.0549% African / African-American · 41/74,682 alleles

Filtering AF 0.0415% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0369%

Overall 0.00267% 43/1,607,672 alleles · ultra-rare exomes 27/1,455,406 · genomes 16/152,266 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0549%	1,822
Remaining individualsnot grpmax-eligible	0.00321%	31,144

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.Ile439Phe
Coding: c.1315A>T
MANE Select: NM_014813
dbSNP: rs568784194
Type: single nucleotide variant
Location: chr1:113107595 (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
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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-ile439phe (accessed [today's date]).

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