Is LAMC2 p.Lys256= (c.768A>G) pathogenic?

LAMC2 p.Lys256= (c.768A>G) is classified Likely benign in LAMC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-31). Very rare (popmax 0.00167%, amr).

How common is LAMC2 p.Lys256= (c.768A>G) in the general population?

LAMC2 p.Lys256= (c.768A>G) is very rare (popmax 0.00167%, amr) (gnomAD).

LAMC2 p.Lys256=

c.768A>G · rs143871142 · VCV1158457

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.23	acceptor loss, 19 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 1.5	GERP -0.48, phastCons 1
Overall
CADD	9.223	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,006 alleles

Filtering AF 0.000803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00065%

Overall 0.00124% 20/1,613,918 alleles · very rare exomes 17/1,461,784 · genomes 3/152,134 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0048%	20,829
Admixed Americangrpmax	0.00167%	60,006
European (non-Finnish)	0.00136%	73,751

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Lys256=
Coding: c.768A>G
MANE Select: NM_005562
dbSNP: rs143871142
Type: single nucleotide variant
Location: chr1:183223139 (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

Similar variants

LAMC2 p.Lys256Arg Uncertain significance ★ ⚠ same residue
LAMC2 p.Lys256Ile Uncertain significance ★ same residue
LAMC2 c.1715-2A>G Likely pathogenic ★★ same type
LAMC2 c.268+1G>A Likely pathogenic ★★ same type
LAMC2 c.3328+1G>A Pathogenic/Likely pathogenic ★★ same type
LAMC2 c.640+1G>A Likely pathogenic ★★ same type
LAMC2 p.Arg1129Ter Pathogenic ★★ same type
LAMC2 p.Arg115Ter Pathogenic ★★ 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/lamc2-p-lys256 (accessed [today's date]).

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