Is LAMC2 p.Thr1069Met (c.3206C>T) pathogenic?

LAMC2 p.Thr1069Met (c.3206C>T) is classified Benign/Likely benign in LAMC2 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.0725); Rare (popmax 0.871%, sas); Associated with junctional epidermolysis bullosa.

What condition is associated with LAMC2 p.Thr1069Met (c.3206C>T)?

LAMC2 p.Thr1069Met (c.3206C>T) is associated with junctional epidermolysis bullosa (ClinVar).

How common is LAMC2 p.Thr1069Met (c.3206C>T) in the general population?

LAMC2 p.Thr1069Met (c.3206C>T) is rare (popmax 0.871%, sas) (gnomAD).

What do computational predictors say about LAMC2 p.Thr1069Met (c.3206C>T)?

AlphaMissense predicts likely benign (score 0.0725) — an in-silico prediction, not a clinical call.

LAMC2 p.Thr1069Met

c.3206C>T · rs139043074 · VCV195603

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

AlphaMissense

likely benign

0.0725 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.871%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

junctional epidermolysis bullosa

Computational evidence

Protein change
AlphaMissense	0.0725	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -7.50	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 -4.3	GERP -4
Regional constraint	o/e 1.00	unconstrained · MANE · 11 kb · p 0.91 · regional, not allelic
Overall
CADD	0.035	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 0.871% South Asian · 793/91,090 alleles

Filtering AF 0.82% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.8%

Overall 0.126% 2,036/1,614,172 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.871%	115
Middle Eastern	0.511%	196
Remaining individualsnot grpmax-eligible	0.136%	735
European (non-Finnish)	0.0889%	1,125
Ashkenazi Jewishnot grpmax-eligible	0.0777%	1,287
Admixed American	0.0533%	1,876
African / African-American	0.0227%	4,414
Finnishnot grpmax-eligible	0.00781%	12,803
East Asian	0.00223%	44,888

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.Thr1069Met
Coding: c.3206C>T
MANE Select: NM_005562
dbSNP: rs139043074
Type: single nucleotide variant
Location: chr1:183240176 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 1069: the 'domain ii and i' region

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

Disease context

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

Similar variants

LAMC2 p.Thr1069= Likely benign ★ same residue
LAMC2 p.Arg1129Ter Pathogenic ★★ same condition
LAMC2 p.Arg170Ter Pathogenic/Likely pathogenic ★★ same condition
LAMC2 p.Arg245Ter Pathogenic/Likely pathogenic ★★ same condition
LAMC2 p.Arg349Ter Pathogenic ★★ same condition
LAMC2 p.Gln692Ter Pathogenic/Likely pathogenic ★★ same condition
LAMC2 p.Gln961Ter Pathogenic/Likely pathogenic ★★ same condition
LAMC2 c.503+6T>C 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-thr1069met (accessed [today's date]).

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