Is LCT p.Pro808fs (c.2423del) pathogenic?

LCT p.Pro808fs (c.2423del) is classified Pathogenic in LCT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-16). Very rare (popmax 0.000424%, nfe).

How common is LCT p.Pro808fs (c.2423del) in the general population?

LCT p.Pro808fs (c.2423del) is very rare (popmax 0.000424%, nfe) (gnomAD).

LCT p.Pro808fs

c.2423del · VCV3643650

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000424%, nfe)

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 0.52	GERP -1.3, phastCons 0.98
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000424% European (non-Finnish) · 5/1,180,052 alleles

Filtering AF 0.000124% ClinGen BA1/BS1 input FAF95, joint · FAF99 9e-05%

Overall 0.00031% 5/1,614,142 alleles · very rare exomes 4/1,461,874 · genomes 1/152,268 · joint denominator

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: LCT
Protein: p.Pro808fs
Coding: c.2423del
MANE Select: NM_002299
Type: Deletion
Location: chr2:135809924 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 808: the 'glycosyl hydrolase-1 2; region ii' region

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

Similar variants

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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-pro808fs (accessed [today's date]).

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