Is LANCL2 p.Pro53Thr (c.157C>A) pathogenic?

LANCL2 p.Pro53Thr (c.157C>A) is classified Uncertain significance in LANCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-15). AlphaMissense: likely benign (0.0596); No allele count reported in gnomAD v4.1 (AN 1,557,346).

How common is LANCL2 p.Pro53Thr (c.157C>A) in the general population?

LANCL2 p.Pro53Thr (c.157C>A) is no allele count reported in gnomAD v4.1 (AN 1,557,346) (gnomAD).

What do computational predictors say about LANCL2 p.Pro53Thr (c.157C>A)?

AlphaMissense predicts likely benign (score 0.0596) — an in-silico prediction, not a clinical call.

LANCL2 p.Pro53Thr

c.157C>A · VCV4046217

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0596 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,557,346)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0596	likely benign
REVEL	0.028	moderately benign-leaning
SaProt	LLR -6.32	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.32	GERP 0.26
Regional constraint	o/e 1.65	unconstrained · MANE · 26 kb · p 8.9e-12 · regional, not allelic
Overall
CADD	3.116	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,557,346). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: LANCL2
Protein: p.Pro53Thr
Coding: c.157C>A
MANE Select: NM_018697
Type: single nucleotide variant
Location: chr7:55366182 (GRCh38)
Gene constraint: LOEUF 0.846 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 92.37 · 1 PDB

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-pro53thr (accessed [today's date]).

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