Is LAMC3 p.Ala975Val (c.2924C>T) pathogenic?

LAMC3 p.Ala975Val (c.2924C>T) is classified Conflicting classifications of pathogenicity in LAMC3 (ClinVar, Conflicting submitters, 3 submitters; last evaluated 2025-07-23). AlphaMissense: likely benign (0.0805); Ultra-rare (popmax 0.0719%, eas); Associated with Inborn genetic diseases.

What condition is associated with LAMC3 p.Ala975Val (c.2924C>T)?

LAMC3 p.Ala975Val (c.2924C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LAMC3 p.Ala975Val (c.2924C>T) in the general population?

LAMC3 p.Ala975Val (c.2924C>T) is ultra-rare (popmax 0.0719%, eas) (gnomAD).

What do computational predictors say about LAMC3 p.Ala975Val (c.2924C>T)?

AlphaMissense predicts likely benign (score 0.0805) — an in-silico prediction, not a clinical call.

LAMC3 p.Ala975Val

c.2924C>T · rs756683242 · VCV493496

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0805 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0719%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0805	likely benign
REVEL	0.075	moderately benign-leaning
SaProt	LLR -5.84	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 1.1	GERP -4, phastCons 0.004
Regional constraint	o/e 0.94	unconstrained · MANE · 83 kb · p 0.0039 · regional, not allelic
Overall
CADD	8.459	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 0.0719% East Asian · 32/44,514 alleles

Filtering AF 0.0523% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0456%

Overall 0.00212% 34/1,603,642 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0719%	1,391
Remaining individualsnot grpmax-eligible	0.00161%	62,046
South Asian	0.00112%	89,168

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.Ala975Val
Coding: c.2924C>T
MANE Select: NM_006059
dbSNP: rs756683242
Type: single nucleotide variant
Location: chr9:131069705 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 975: the laminin egf-like 11 domain

Full LAMC3 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

LAMC3 p.Ala975= Likely benign ★ same residue
LAMC3 p.Gln550Ter Pathogenic ★★ same condition
LAMC3 p.Ser421Ter Pathogenic ★★ same condition
LAMC3 p.Ala109Pro Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala1137Pro Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala1137Thr Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala1161Val Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala1183Thr 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/lamc3-p-ala975val (accessed [today's date]).

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