Is LAMC3 p.Ala48Ser (c.142G>T) pathogenic?

LAMC3 p.Ala48Ser (c.142G>T) is classified Uncertain significance in LAMC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-05). AlphaMissense: likely benign (0.2541); Very rare (popmax 0.000793%, nfe).

How common is LAMC3 p.Ala48Ser (c.142G>T) in the general population?

LAMC3 p.Ala48Ser (c.142G>T) is very rare (popmax 0.000793%, nfe) (gnomAD).

What do computational predictors say about LAMC3 p.Ala48Ser (c.142G>T)?

AlphaMissense predicts likely benign (score 0.2541) — an in-silico prediction, not a clinical call.

LAMC3 p.Ala48Ser

c.142G>T · rs1195853230 · VCV1314436

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2541 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000793%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2541	likely benign
REVEL	0.395	indeterminate
SaProt	LLR -10.74	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 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 83 kb · p 0.0039 · regional, not allelic
Overall
CADD	22.3	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 0.000793% European (non-Finnish) · 9/1,134,814 alleles

Filtering AF 0.000373% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00027%

Overall 0.000597% 9/1,507,854 alleles · very rare exomes 9/1,355,778 · genomes 0/152,076 · joint denominator

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: LAMC3
Protein: p.Ala48Ser
Coding: c.142G>T
MANE Select: NM_006059
dbSNP: rs1195853230
Type: single nucleotide variant
Location: chr9:131009356 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 48: the laminin n-terminal domain

Full LAMC3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LAMC3 c.1166-1G>A Likely pathogenic ★★ same type
LAMC3 c.3211+1G>A Likely pathogenic ★★ same type
LAMC3 c.3211+2T>C Likely pathogenic ★★ same type
LAMC3 c.976+1G>A Pathogenic ★★ same type
LAMC3 p.Cys810Ter Pathogenic ★★ same type
LAMC3 p.Gln550Ter Pathogenic ★★ same type
LAMC3 p.Ser421Ter Pathogenic ★★ same type
LAMC3 p.Ala1090Ser Uncertain significance ★★ ⚠ 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/lamc3-p-ala48ser (accessed [today's date]).

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