Is LANCL1 p.Phe79Ser (c.236T>C) pathogenic?

LANCL1 p.Phe79Ser (c.236T>C) is classified Uncertain significance in LANCL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-07). AlphaMissense: likely benign (0.302); Very rare (popmax 0.00721%, nfe).

How common is LANCL1 p.Phe79Ser (c.236T>C) in the general population?

LANCL1 p.Phe79Ser (c.236T>C) is very rare (popmax 0.00721%, nfe) (gnomAD).

What do computational predictors say about LANCL1 p.Phe79Ser (c.236T>C)?

AlphaMissense predicts likely benign (score 0.302) — an in-silico prediction, not a clinical call.

LANCL1 p.Phe79Ser

c.236T>C · rs372346977 · VCV3117769

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.302 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00721%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.302	likely benign
REVEL	0.16	moderately benign-leaning
SaProt	LLR -7.15	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 9	GERP 2, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 42 kb · p 0.019 · regional, not allelic
Overall
CADD	23.7	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 0.00721% European (non-Finnish) · 85/1,179,568 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00558% 90/1,612,738 alleles · very rare exomes 88/1,461,212 · genomes 2/151,526 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00721%	13,877
Remaining individualsnot grpmax-eligible	0.00481%	20,811
African / African-American	0.00268%	37,318

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: LANCL1
Protein: p.Phe79Ser
Coding: c.236T>C
MANE Select: NM_006055
dbSNP: rs372346977
Type: single nucleotide variant
Location: chr2:210455278 (GRCh38)
Gene constraint: LOEUF 1.304 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.52 · 6 PDB
Residue 79: an α-helix

Full LANCL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LANCL1 p.Arg41= Benign ★★ same type
LANCL1 p.Ala115Val Uncertain significance ★ ⚠ same type
LANCL1 p.Ala117Thr Uncertain significance ★ ⚠ same type
LANCL1 p.Ala118Thr Uncertain significance ★ ⚠ same type
LANCL1 p.Ala147Asp Uncertain significance ★ ⚠ same type
LANCL1 p.Ala18Val Uncertain significance ★ ⚠ same type
LANCL1 p.Ala222Thr Uncertain significance ★ ⚠ same type
LANCL1 p.Ala279Ser 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/lancl1-p-phe79ser (accessed [today's date]).

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