Is LANCL2 p.Arg8Ser (c.24G>C) pathogenic?

LANCL2 p.Arg8Ser (c.24G>C) is classified Uncertain significance in LANCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely pathogenic (0.9481); Ultra-rare (popmax 0.0172%, mid).

How common is LANCL2 p.Arg8Ser (c.24G>C) in the general population?

LANCL2 p.Arg8Ser (c.24G>C) is ultra-rare (popmax 0.0172%, mid) (gnomAD).

What do computational predictors say about LANCL2 p.Arg8Ser (c.24G>C)?

AlphaMissense predicts likely pathogenic (score 0.9481) — an in-silico prediction, not a clinical call.

LANCL2 p.Arg8Ser

c.24G>C · VCV3537243

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9481 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0172%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9481	likely pathogenic
REVEL	0.268	benign-leaning
SaProt	LLR -9.42	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.027	GERP -2, phastCons 0.14
Regional constraint	o/e 1.65	unconstrained · MANE · 26 kb · p 8.9e-12 · regional, not allelic
Overall
CADD	19.16	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 0.0172% Middle Eastern · 1/5,810 alleles

Filtering AF 0.0121% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0114%

Overall 0.0108% 164/1,515,266 alleles · ultra-rare exomes 158/1,363,014 · genomes 6/152,252 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0172%	5,810
European (non-Finnish)	0.0139%	7,177
Remaining individualsnot grpmax-eligible	0.00517%	19,328
African / African-American	0.00428%	23,339

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: LANCL2
Protein: p.Arg8Ser
Coding: c.24G>C
MANE Select: NM_018697
Type: single nucleotide variant
Location: chr7:55366049 (GRCh38)
Gene constraint: LOEUF 0.846 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.37 · 1 PDB
Residue 8: the 'interaction with inositol phospholipids' region

Full LANCL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LANCL2 p.Ala277Val Uncertain significance ★ ⚠ same type
LANCL2 p.Ala334Val Uncertain significance ★ ⚠ same type
LANCL2 p.Ala35Pro Uncertain significance ★ ⚠ same type
LANCL2 p.Ala37Glu Uncertain significance ★ ⚠ same type
LANCL2 p.Ala424Thr Uncertain significance ★ ⚠ same type
LANCL2 p.Ala44Val Uncertain significance ★ ⚠ same type
LANCL2 p.Arg128Gln Uncertain significance ★ ⚠ same type
LANCL2 p.Arg183Ile 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/lancl2-p-arg8ser (accessed [today's date]).

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