Is LAMC3 p.Pro618Ser (c.1852C>T) pathogenic?

LAMC3 p.Pro618Ser (c.1852C>T) is classified Uncertain significance in LAMC3 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-09-04). AlphaMissense: likely benign (0.0853); Very rare (popmax 0.00167%, amr).

How common is LAMC3 p.Pro618Ser (c.1852C>T) in the general population?

LAMC3 p.Pro618Ser (c.1852C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about LAMC3 p.Pro618Ser (c.1852C>T)?

AlphaMissense predicts likely benign (score 0.0853) — an in-silico prediction, not a clinical call.

LAMC3 p.Pro618Ser

c.1852C>T · rs749305389 · VCV1307474

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0853 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0853	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -11.79	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.17	GERP -0.51
Regional constraint	o/e 0.94	unconstrained · MANE · 83 kb · p 0.0039 · regional, not allelic
Overall
CADD	15.8	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 0.00167% Admixed American · 1/60,012 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000186% 3/1,613,790 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,012
European (non-Finnish)	0.00017%	589,971

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.Pro618Ser
Coding: c.1852C>T
MANE Select: NM_006059
dbSNP: rs749305389
Type: single nucleotide variant
Location: chr9:131052878 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 618: the laminin iv type a 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-pro618ser (accessed [today's date]).

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