Is LCT p.Arg1908Cys (c.5722C>T) pathogenic?

LCT p.Arg1908Cys (c.5722C>T) is classified Conflicting classifications of pathogenicity in LCT (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2024-09-20). AlphaMissense: likely benign (0.0871); Ultra-rare (popmax 0.034%, sas); Associated with congenital lactase deficiency.

What condition is associated with LCT p.Arg1908Cys (c.5722C>T)?

LCT p.Arg1908Cys (c.5722C>T) is associated with congenital lactase deficiency (ClinVar).

How common is LCT p.Arg1908Cys (c.5722C>T) in the general population?

LCT p.Arg1908Cys (c.5722C>T) is ultra-rare (popmax 0.034%, sas) (gnomAD).

How is Congenital lactase deficiency inherited?

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

What do computational predictors say about LCT p.Arg1908Cys (c.5722C>T)?

AlphaMissense predicts likely benign (score 0.0871) — an in-silico prediction, not a clinical call.

LCT p.Arg1908Cys

c.5722C>T · rs138964370 · VCV1025930

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0871 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

congenital lactase deficiency

Computational evidence

Protein change
AlphaMissense	0.0871	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -7.51	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 -0.009	GERP -4.8
Regional constraint	o/e 0.69	unconstrained · MANE · 19 kb · p 6.6e-18 · regional, not allelic
Overall
CADD	7.987	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.034% South Asian · 31/91,086 alleles

Filtering AF 0.0246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0214%

Overall 0.0139% 224/1,614,022 alleles · ultra-rare exomes 207/1,461,834 · genomes 17/152,188 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.05%	2,001
Remaining individualsnot grpmax-eligible	0.0384%	2,604
South Asiangrpmax	0.034%	2,938
East Asian	0.0245%	4,081
Middle Eastern	0.0165%	6,066
European (non-Finnish)	0.0106%	9,440

Finnish 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.Arg1908Cys
Coding: c.5722C>T
MANE Select: NM_002299
dbSNP: rs138964370
Type: single nucleotide variant
Location: chr2:135788386 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 1908: 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 p.Arg1908His Uncertain significance ★ ⚠ same residue
LCT p.Arg1908Ser Uncertain significance ★ ⚠ same residue
LCT p.Arg1908= Likely benign ★ same residue
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

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-arg1908cys (accessed [today's date]).

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