Is LCT p.Arg1908Ser (c.5722C>A) pathogenic?

LCT p.Arg1908Ser (c.5722C>A) is classified Uncertain significance in LCT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-21). AlphaMissense: likely benign (0.129); Absent from gnomAD v4.1.

How common is LCT p.Arg1908Ser (c.5722C>A) in the general population?

LCT p.Arg1908Ser (c.5722C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LCT p.Arg1908Ser (c.5722C>A)?

AlphaMissense predicts likely benign (score 0.129) — an in-silico prediction, not a clinical call.

LCT p.Arg1908Ser

c.5722C>A · rs138964370 · VCV1722137

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.129 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.129	likely benign
REVEL	0.042	moderately benign-leaning
SaProt	LLR -6.58	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	0.591	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: LCT
Protein: p.Arg1908Ser
Coding: c.5722C>A
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

Similar variants

LCT p.Arg1908Cys Conflicting classifications of pathogenicity ★ ⚠ same residue
LCT p.Arg1908His Uncertain significance ★ ⚠ same residue
LCT p.Arg1908= Likely benign ★ same residue
LCT c.4866+2T>G Likely pathogenic ★★ same type
LCT p.Gln1179Ter Pathogenic/Likely pathogenic ★★ same type
LCT p.Lys787Ter Pathogenic/Likely pathogenic ★★ same type
LCT p.Tyr1390Ter Pathogenic ★★ same type
LCT c.4173+5G>A Uncertain significance ★★ 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-arg1908ser (accessed [today's date]).

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