Is LCT p.Arg371= (c.1113G>A) pathogenic?

LCT p.Arg371= (c.1113G>A) is classified Conflicting classifications of pathogenicity in LCT (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-02-02). Rare (popmax 0.231%, mid); Associated with congenital lactase deficiency.

What condition is associated with LCT p.Arg371= (c.1113G>A)?

LCT p.Arg371= (c.1113G>A) is associated with congenital lactase deficiency (ClinVar).

How common is LCT p.Arg371= (c.1113G>A) in the general population?

LCT p.Arg371= (c.1113G>A) is rare (popmax 0.231%, mid) (gnomAD).

How is Congenital lactase deficiency inherited?

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

LCT p.Arg371=

c.1113G>A · rs148142216 · VCV729578

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

rare (popmax 0.231%, mid)

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 -0.23	GERP -3.6
Overall
CADD	1.172	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.231% Middle Eastern · 14/6,060 alleles

Filtering AF 0.158% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.155%

Overall 0.156% 2,511/1,614,006 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.817%	122
Middle Easterngrpmax	0.231%	433
Admixed American	0.177%	566
Remaining individualsnot grpmax-eligible	0.171%	584
European (non-Finnish)	0.164%	610
Finnishnot grpmax-eligible	0.0971%	1,030
South Asian	0.0274%	3,643
African / African-American	0.0227%	4,414
East Asian	0.00446%	22,436

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg371=
Coding: c.1113G>A
MANE Select: NM_002299
dbSNP: rs148142216
Type: single nucleotide variant
Location: chr2:135817935 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 371: the 'glycosyl hydrolase-1 2; region ii' 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-arg371 (accessed [today's date]).

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