Is LRIG2 p.Arg977Ser (c.2931G>T) pathogenic?

LRIG2 p.Arg977Ser (c.2931G>T) is classified Uncertain significance in LRIG2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely benign (0.2724); Very rare (popmax 0.00801%, afr).

How common is LRIG2 p.Arg977Ser (c.2931G>T) in the general population?

LRIG2 p.Arg977Ser (c.2931G>T) is very rare (popmax 0.00801%, afr) (gnomAD).

What do computational predictors say about LRIG2 p.Arg977Ser (c.2931G>T)?

AlphaMissense predicts likely benign (score 0.2724) — an in-silico prediction, not a clinical call.

LRIG2 p.Arg977Ser

c.2931G>T · VCV4099618

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2724 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00801%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2724	likely benign
REVEL	0.287	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 4.6	GERP -0.27, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 14 kb · p 0.0085 · regional, not allelic
Overall
CADD	19.0	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 0.00801% African / African-American · 6/74,898 alleles

Filtering AF 0.00347% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00229%

Overall 0.000372% 6/1,614,026 alleles · very rare exomes 1/1,461,878 · genomes 5/152,148 · joint denominator

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.Arg977Ser
Coding: c.2931G>T
MANE Select: NM_014813
Type: single nucleotide variant
Location: chr1:113119483 (GRCh38)
Gene constraint: LOEUF 0.95 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.87
Residue 977: the 'disordered' region

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-arg977ser (accessed [today's date]).

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