Is LAMC2 p.Ser34Phe (c.101C>T) pathogenic?

LAMC2 p.Ser34Phe (c.101C>T) is classified Uncertain significance in LAMC2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-22). AlphaMissense: likely pathogenic (0.9288); Ultra-rare (popmax 0.0165%, mid); Associated with Inborn genetic diseases.

What condition is associated with LAMC2 p.Ser34Phe (c.101C>T)?

LAMC2 p.Ser34Phe (c.101C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LAMC2 p.Ser34Phe (c.101C>T) in the general population?

LAMC2 p.Ser34Phe (c.101C>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about LAMC2 p.Ser34Phe (c.101C>T)?

AlphaMissense predicts likely pathogenic (score 0.9288) — an in-silico prediction, not a clinical call.

LAMC2 p.Ser34Phe

c.101C>T · VCV4623514

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9288 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9288	likely pathogenic · top 6% in LAMC2
REVEL	0.534	indeterminate
SaProt	LLR -16.80	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 45 kb · p 0.031 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0165% Middle Eastern · 1/6,064 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0009%

Overall 0.00143% 23/1,608,834 alleles · ultra-rare exomes 20/1,461,142 · genomes 3/147,692 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,064
European (non-Finnish)	0.0017%	58,964
Remaining individualsnot grpmax-eligible	0.0016%	62,376
African / African-American	0.00137%	72,852

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: LAMC2
Protein: p.Ser34Phe
Coding: c.101C>T
MANE Select: NM_005562
Type: single nucleotide variant
Location: chr1:183207902 (GRCh38)
Gene constraint: LOEUF 0.797 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 72.89
Residue 34: the laminin egf-like 1 domain

Full LAMC2 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

LAMC2 p.Asp247His Uncertain significance ★★ ⚠ same condition
LAMC2 p.Gln1005Arg Uncertain significance ★★ ⚠ same condition
LAMC2 p.Glu1160Asp Uncertain significance ★★ ⚠ same condition
LAMC2 p.Gly278Arg Uncertain significance ★★ ⚠ same condition
LAMC2 p.Gly672Ala Uncertain significance ★★ ⚠ same condition
LAMC2 p.His1107Arg Uncertain significance ★★ ⚠ same condition
LAMC2 p.Ile447Val Uncertain significance ★★ ⚠ same condition
LAMC2 p.Ile839Ser 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/lamc2-p-ser34phe (accessed [today's date]).

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