Is LAMC2 p.Lys256Arg (c.767A>G) pathogenic?

LAMC2 p.Lys256Arg (c.767A>G) is classified Uncertain significance in LAMC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-18). AlphaMissense: likely benign (0.0807); Ultra-rare (popmax 0.033%, mid); Associated with Inborn genetic diseases.

What condition is associated with LAMC2 p.Lys256Arg (c.767A>G)?

LAMC2 p.Lys256Arg (c.767A>G) is associated with Inborn genetic diseases (ClinVar).

How common is LAMC2 p.Lys256Arg (c.767A>G) in the general population?

LAMC2 p.Lys256Arg (c.767A>G) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about LAMC2 p.Lys256Arg (c.767A>G)?

AlphaMissense predicts likely benign (score 0.0807) — an in-silico prediction, not a clinical call.

LAMC2 p.Lys256Arg

c.767A>G · VCV4096478

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0807 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0807	likely benign
REVEL	0.061	moderately benign-leaning
SaProt	LLR -6.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.46	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 4.7	GERP -1.6, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.031 · regional, not allelic
Overall
CADD	22.8	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 0.033% Middle Eastern · 2/6,054 alleles

Filtering AF 0.00583% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0038%

Overall 0.00229% 37/1,614,020 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,027
Admixed American	0.0117%	8,576
Remaining individualsnot grpmax-eligible	0.008%	12,501
East Asian	0.00446%	22,433
African / African-American	0.004%	25,005
South Asian	0.00329%	30,359
European (non-Finnish)	0.00127%	78,666

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: LAMC2
Protein: p.Lys256Arg
Coding: c.767A>G
MANE Select: NM_005562
Type: single nucleotide variant
Location: chr1:183223138 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 256: 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.Lys256Ile Uncertain significance ★ same residue
LAMC2 p.Lys256= Likely benign ★ same residue
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

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-lys256arg (accessed [today's date]).

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