Is LCT p.Phe847fs (c.2540del) pathogenic?

LCT p.Phe847fs (c.2540del) is classified Pathogenic in LCT (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-12). Absent from gnomAD.

How common is LCT p.Phe847fs (c.2540del) in the general population?

LCT p.Phe847fs (c.2540del) is absent from gnomAD (gnomAD).

LCT p.Phe847fs

c.2540del · rs2467219547 · VCV2855669

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 8 of 17
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 1.5	GERP -0.24, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. 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: LCT
Protein: p.Phe847fs
Coding: c.2540del
MANE Select: NM_002299
dbSNP: rs2467219547
Type: Deletion
Location: chr2:135809807 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 847: the 'glycosyl hydrolase-1 2; region ii' region

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

Similar variants

LCT c.4977-18_4977-16del Likely benign ★★ same type
LCT c.5111+1del Pathogenic ★ same type
LCT p.Asn1656fs Pathogenic ★ same type
LCT p.Glu761fs Pathogenic ★ same type
LCT p.Leu1442fs Pathogenic ★ same type
LCT p.Leu195fs Likely pathogenic ★ same type
LCT p.Phe71fs Pathogenic ★ same type
LCT p.Phe738fs Likely pathogenic ★ 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/lct-p-phe847fs (accessed [today's date]).

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