Is LCT p.Pro1843= (c.5529C>T) pathogenic?

LCT p.Pro1843= (c.5529C>T) is classified Conflicting classifications of pathogenicity in LCT (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-10-03). Very rare (popmax 0.00223%, eas); Associated with congenital lactase deficiency.

What condition is associated with LCT p.Pro1843= (c.5529C>T)?

LCT p.Pro1843= (c.5529C>T) is associated with congenital lactase deficiency (ClinVar).

How common is LCT p.Pro1843= (c.5529C>T) in the general population?

LCT p.Pro1843= (c.5529C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Congenital lactase deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

LCT p.Pro1843=

c.5529C>T · rs761696901 · VCV331165

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

congenital lactase deficiency

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.1	GERP -3.9
Overall
CADD	2.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,892 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00161% 26/1,613,706 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,892
European (non-Finnish)	0.00186%	53,628
Remaining individualsnot grpmax-eligible	0.0016%	62,472
African / African-American	0.00133%	74,910
South Asian	0.0011%	91,066

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.Pro1843=
Coding: c.5529C>T
MANE Select: NM_002299
dbSNP: rs761696901
Type: single nucleotide variant
Location: chr2:135789605 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 1843: the 'glycosyl hydrolase-1 4; region iv. lactase activity' region; the 'required for homodimerization and transport to the plasma membrane' region

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

Disease context

congenital lactase deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital lactase deficiency (Orphanet):

Inheritance: Autosomal recessive

Similar variants

LCT c.4866+2T>G Likely pathogenic ★★ same condition
LCT p.Gln1179Ter Pathogenic/Likely pathogenic ★★ same condition
LCT p.Tyr1390Ter Pathogenic ★★ same condition
LCT c.4173+5G>A Uncertain significance ★★ same condition
LCT p.Ala94Thr Uncertain significance ★★ ⚠ same condition
LCT p.Gln594Glu Uncertain significance ★★ ⚠ same condition
LCT p.Gly1400Ser Uncertain significance ★★ ⚠ same condition
LCT p.Gly215Arg Uncertain significance ★★ ⚠ same condition

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-pro1843 (accessed [today's date]).

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