Is LAMC3 p.Pro57Ser (c.169C>T) pathogenic?

LAMC3 p.Pro57Ser (c.169C>T) is classified Uncertain significance in LAMC3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-15). AlphaMissense: likely benign (0.1763); Very rare (popmax 8.76e-05%, nfe).

How common is LAMC3 p.Pro57Ser (c.169C>T) in the general population?

LAMC3 p.Pro57Ser (c.169C>T) is very rare (popmax 8.76e-05%, nfe) (gnomAD).

What do computational predictors say about LAMC3 p.Pro57Ser (c.169C>T)?

AlphaMissense predicts likely benign (score 0.1763) — an in-silico prediction, not a clinical call.

LAMC3 p.Pro57Ser

c.169C>T · rs1363370959 · VCV1509435

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1763 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.76e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1763	likely benign
REVEL	0.379	indeterminate
SaProt	LLR -12.70	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 7.2	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 83 kb · p 0.0039 · regional, not allelic
Overall
CADD	24.3	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 8.76e-05% European (non-Finnish) · 1/1,141,858 alleles

Overall 6.54e-05% 1/1,528,112 alleles · very rare exomes 0/1,376,114 · genomes 1/151,998 · 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.Pro57Ser
Coding: c.169C>T
MANE Select: NM_006059
dbSNP: rs1363370959
Type: single nucleotide variant
Location: chr9:131009383 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 57: the laminin n-terminal domain

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

Similar variants

LAMC3 p.Pro57= Likely benign ★ same residue
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

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-pro57ser (accessed [today's date]).

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