Is LAMC2 p.Ala144Pro (c.430G>C) pathogenic?

LAMC2 p.Ala144Pro (c.430G>C) is classified Uncertain significance in LAMC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-22). AlphaMissense: likely benign (0.2515); Ultra-rare (popmax 0.078%, eas); Associated with Inborn genetic diseases.

What condition is associated with LAMC2 p.Ala144Pro (c.430G>C)?

LAMC2 p.Ala144Pro (c.430G>C) is associated with Inborn genetic diseases (ClinVar).

How common is LAMC2 p.Ala144Pro (c.430G>C) in the general population?

LAMC2 p.Ala144Pro (c.430G>C) is ultra-rare (popmax 0.078%, eas) (gnomAD).

What do computational predictors say about LAMC2 p.Ala144Pro (c.430G>C)?

AlphaMissense predicts likely benign (score 0.2515) — an in-silico prediction, not a clinical call.

LAMC2 p.Ala144Pro

c.430G>C · rs370492230 · VCV2492063

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2515 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.078%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2515	likely benign
REVEL	0.392	indeterminate
SaProt	LLR -12.09	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP -0.27, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.031 · regional, not allelic
Overall
CADD	25.2	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 0.078% East Asian · 35/44,890 alleles

Filtering AF 0.0576% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0506%

Overall 0.00235% 38/1,614,176 alleles · ultra-rare exomes 33/1,461,842 · genomes 5/152,334 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.078%	1,283
Remaining individualsnot grpmax-eligible	0.0032%	31,252
Admixed American	0.00167%	60,024

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.Ala144Pro
Coding: c.430G>C
MANE Select: NM_005562
dbSNP: rs370492230
Type: single nucleotide variant
Location: chr1:183218415 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 144: the laminin egf-like 3 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-ala144pro (accessed [today's date]).

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