Is LANCL2 p.Thr55Pro (c.163A>C) pathogenic?

LANCL2 p.Thr55Pro (c.163A>C) is classified Uncertain significance in LANCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-28). AlphaMissense: likely benign (0.0587); Ultra-rare (popmax 0.0172%, eas).

How common is LANCL2 p.Thr55Pro (c.163A>C) in the general population?

LANCL2 p.Thr55Pro (c.163A>C) is ultra-rare (popmax 0.0172%, eas) (gnomAD).

What do computational predictors say about LANCL2 p.Thr55Pro (c.163A>C)?

AlphaMissense predicts likely benign (score 0.0587) — an in-silico prediction, not a clinical call.

LANCL2 p.Thr55Pro

c.163A>C · rs1219770907 · VCV3117780

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0587 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0172%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0587	likely benign
REVEL	0.038	moderately benign-leaning
SaProt	LLR -5.92	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 -2.8	GERP -2.5
Regional constraint	o/e 1.65	unconstrained · MANE · 26 kb · p 8.9e-12 · regional, not allelic
Overall
CADD	0.115	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

Grpmax group 0.0172% East Asian · 7/40,662 alleles

Filtering AF 0.00803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00567%

Overall 0.000581% 9/1,550,228 alleles · ultra-rare exomes 7/1,397,952 · genomes 2/152,276 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0172%	5,809
European (non-Finnish)	0.000175%	572,898

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.Thr55Pro
Coding: c.163A>C
MANE Select: NM_018697
dbSNP: rs1219770907
Type: single nucleotide variant
Location: chr7:55366188 (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-thr55pro (accessed [today's date]).

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