Is LAMC3 p.Ser1124Phe (c.3371C>T) pathogenic?

LAMC3 p.Ser1124Phe (c.3371C>T) is classified Benign/Likely benign in LAMC3 (ClinVar, Multiple submitters, 8 submitters; last evaluated 2026-06-01). AlphaMissense: likely benign (0.1631); Low-frequency (popmax 1.07%, nfe); Associated with occipital pachygyria and polymicrogyria.

What condition is associated with LAMC3 p.Ser1124Phe (c.3371C>T)?

LAMC3 p.Ser1124Phe (c.3371C>T) is associated with occipital pachygyria and polymicrogyria (ClinVar).

How common is LAMC3 p.Ser1124Phe (c.3371C>T) in the general population?

LAMC3 p.Ser1124Phe (c.3371C>T) is low-frequency (popmax 1.07%, nfe) (gnomAD).

What do computational predictors say about LAMC3 p.Ser1124Phe (c.3371C>T)?

AlphaMissense predicts likely benign (score 0.1631) — an in-silico prediction, not a clinical call.

LAMC3 p.Ser1124Phe

c.3371C>T · rs113259170 · VCV129461

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 8 submitters

AlphaMissense

likely benign

0.1631 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.07%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

occipital pachygyria and polymicrogyria

Computational evidence

Protein change
AlphaMissense	0.1631	likely benign
REVEL	0.085	moderately benign-leaning
SaProt	LLR -7.52	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 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 83 kb · p 0.0039 · regional, not allelic
Overall
CADD	25.1	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 1.07% European (non-Finnish) · 12,611/1,179,748 alleles

Filtering AF 1.05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.05%

Overall 0.921% 14,859/1,613,338 alleles · low-frequency exomes 13,761/1,461,062 · genomes 1,098/152,276 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.97%	51
Remaining individualsnot grpmax-eligible	1.09%	91
European (non-Finnish)grpmax	1.07%	94
Middle Eastern	0.759%	132
Finnishnot grpmax-eligible	0.673%	149
Admixed American	0.534%	187
African / African-American	0.145%	688
South Asian	0.0837%	1,195

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser1124Phe
Coding: c.3371C>T
MANE Select: NM_006059
dbSNP: rs113259170
Type: single nucleotide variant
Location: chr9:131072789 (GRCh38)
Gene constraint: LOEUF 0.909 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.23
Residue 1124: the 'domain ii and i' region

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

Disease context

occipital pachygyria and polymicrogyria — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LAMC3 p.Ser1124Cys Uncertain significance ★ ⚠ same residue
LAMC3 p.Ser1124= Likely benign ★ same residue
LAMC3 c.1166-1G>A Likely pathogenic ★★ same condition
LAMC3 c.3211+2T>C Likely pathogenic ★★ same condition
LAMC3 p.Ala1090Thr Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala1163Thr Uncertain significance ★★ ⚠ same condition
LAMC3 p.Ala79Val Uncertain significance ★★ ⚠ same condition
LAMC3 p.Arg1167Gly 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-ser1124phe (accessed [today's date]).

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