Is LAMC2 p.Ile296Phe (c.886A>T) pathogenic?

LAMC2 p.Ile296Phe (c.886A>T) is classified Uncertain significance in LAMC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-03). AlphaMissense: ambiguous (0.3879); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LAMC2 p.Ile296Phe (c.886A>T)?

LAMC2 p.Ile296Phe (c.886A>T) is associated with Inborn genetic diseases (ClinVar).

How common is LAMC2 p.Ile296Phe (c.886A>T) in the general population?

LAMC2 p.Ile296Phe (c.886A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LAMC2 p.Ile296Phe (c.886A>T)?

AlphaMissense predicts ambiguous (score 0.3879) — an in-silico prediction, not a clinical call.

LAMC2 p.Ile296Phe

c.886A>T · VCV4623530

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3879 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3879	ambiguous
REVEL	0.127	moderately benign-leaning
SaProt	LLR -11.35	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.19	GERP -2.6
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.031 · regional, not allelic
Overall
CADD	18.75	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LAMC2
Protein: p.Ile296Phe
Coding: c.886A>T
MANE Select: NM_005562
Type: single nucleotide variant
Location: chr1:183223257 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 296: the laminin iv type a domain

Full LAMC2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LAMC2 p.Asp247His Uncertain significance ★★ ⚠ same condition
LAMC2 p.Gln1005Arg Uncertain significance ★★ ⚠ same condition
LAMC2 p.Glu1160Asp Uncertain significance ★★ ⚠ same condition
LAMC2 p.Gly278Arg Uncertain significance ★★ ⚠ same condition
LAMC2 p.Gly672Ala Uncertain significance ★★ ⚠ same condition
LAMC2 p.His1107Arg Uncertain significance ★★ ⚠ same condition
LAMC2 p.Ile447Val Uncertain significance ★★ ⚠ same condition
LAMC2 p.Ile839Ser Uncertain significance ★★ ⚠ 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/lamc2-p-ile296phe (accessed [today's date]).

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