Is LANCL2 p.Ser41Phe (c.122C>T) pathogenic?

LANCL2 p.Ser41Phe (c.122C>T) is classified Uncertain significance in LANCL2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-14). AlphaMissense: likely benign (0.1447); Very rare (popmax 0.00119%, sas).

How common is LANCL2 p.Ser41Phe (c.122C>T) in the general population?

LANCL2 p.Ser41Phe (c.122C>T) is very rare (popmax 0.00119%, sas) (gnomAD).

What do computational predictors say about LANCL2 p.Ser41Phe (c.122C>T)?

AlphaMissense predicts likely benign (score 0.1447) — an in-silico prediction, not a clinical call.

LANCL2 p.Ser41Phe

c.122C>T · rs1168974723 · VCV2496521

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1447 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00119%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1447	likely benign
REVEL	0.049	moderately benign-leaning
SaProt	LLR -8.67	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 0.37	GERP 0.02
Regional constraint	o/e 1.65	unconstrained · MANE · 26 kb · p 8.9e-12 · regional, not allelic
Overall
CADD	16.99	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 0.00119% South Asian · 1/84,032 alleles

Filtering AF 0.000128% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.3e-05%

Overall 0.000387% 6/1,551,150 alleles · very rare exomes 6/1,398,782 · genomes 0/152,368 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00119%	84,032
European (non-Finnish)	0.000436%	229,278

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.Ser41Phe
Coding: c.122C>T
MANE Select: NM_018697
dbSNP: rs1168974723
Type: single nucleotide variant
Location: chr7:55366147 (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-ser41phe (accessed [today's date]).

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