Is LAMC2 p.Arg857Pro (c.2570G>C) pathogenic?

LAMC2 p.Arg857Pro (c.2570G>C) is classified Benign/Likely benign in LAMC2 (ClinVar, Multiple submitters, 6 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.142); Rare (popmax 0.692%, nfe); Associated with epidermolysis bullosa, junctional 3A, intermediate.

What condition is associated with LAMC2 p.Arg857Pro (c.2570G>C)?

LAMC2 p.Arg857Pro (c.2570G>C) is associated with epidermolysis bullosa, junctional 3A, intermediate, junctional epidermolysis bullosa Herlitz type, junctional epidermolysis bullosa (ClinVar).

How common is LAMC2 p.Arg857Pro (c.2570G>C) in the general population?

LAMC2 p.Arg857Pro (c.2570G>C) is rare (popmax 0.692%, nfe) (gnomAD).

What do computational predictors say about LAMC2 p.Arg857Pro (c.2570G>C)?

AlphaMissense predicts likely benign (score 0.142) — an in-silico prediction, not a clinical call.

LAMC2 p.Arg857Pro

c.2570G>C · rs144908769 · VCV294009

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.142 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.692%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

epidermolysis bullosa, junctional 3A, intermediate

Computational evidence

Protein change
AlphaMissense	0.142	likely benign
REVEL	0.11	moderately benign-leaning
SaProt	LLR -8.79	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 6.1	GERP -0.21, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.91 · regional, not allelic
Overall
CADD	19.63	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

Grpmax group 0.692% European (non-Finnish) · 8,160/1,180,010 alleles

Filtering AF 0.679% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.674%

Overall 0.563% 9,080/1,614,086 alleles · rare exomes 8,436/1,461,858 · genomes 644/152,228 · joint denominator

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	2.19%	46
European (non-Finnish)grpmax	0.692%	145
Remaining individualsnot grpmax-eligible	0.541%	185
Finnishnot grpmax-eligible	0.444%	225
Admixed American	0.265%	377
African / African-American	0.109%	915
Ashkenazi Jewishnot grpmax-eligible	0.054%	1,850
South Asian	0.0198%	5,060
Middle Eastern	0.0165%	6,060
East Asian	0.00446%	22,437

Amish 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.Arg857Pro
Coding: c.2570G>C
MANE Select: NM_005562
dbSNP: rs144908769
Type: single nucleotide variant
Location: chr1:183236573 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 857: the 'domain ii and i' region

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

Disease context

epidermolysis bullosa, junctional 3A, intermediate — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: junctional epidermolysis bullosa Herlitz type junctional epidermolysis bullosa epidermolysis bullosa, junctional 3B, severe

Similar variants

LAMC2 p.Arg857Gly Uncertain significance ★ ⚠ same residue
LAMC2 p.Arg857Trp Uncertain significance ★ ⚠ same residue
LAMC2 p.Arg857= Likely benign ★ same residue
LAMC2 c.1715-2A>G Likely pathogenic ★★ same condition
LAMC2 c.268+1G>A Likely pathogenic ★★ same condition
LAMC2 c.3328+1G>A Pathogenic/Likely pathogenic ★★ same condition
LAMC2 c.640+1G>A Likely pathogenic ★★ same condition
LAMC2 p.Arg1129Ter Pathogenic ★★ 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-arg857pro (accessed [today's date]).

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