Is LCT p.Asp482Val (c.1445A>T) pathogenic?

LCT p.Asp482Val (c.1445A>T) is classified Uncertain significance in LCT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-06-09). AlphaMissense: likely benign (0.2271); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LCT p.Asp482Val (c.1445A>T)?

LCT p.Asp482Val (c.1445A>T) is associated with Inborn genetic diseases (ClinVar).

How common is LCT p.Asp482Val (c.1445A>T) in the general population?

LCT p.Asp482Val (c.1445A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LCT p.Asp482Val (c.1445A>T)?

AlphaMissense predicts likely benign (score 0.2271) — an in-silico prediction, not a clinical call.

LCT p.Asp482Val

c.1445A>T · rs2467231309 · VCV2294893

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2271 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2271	likely benign
REVEL	0.422	indeterminate
SaProt	LLR -11.51	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5	GERP 1.9, phastCons 0.93
Regional constraint	o/e 0.62	unconstrained · MANE · 5,037 bp · p 1.3e-10 · regional, not allelic
Overall
CADD	23.5	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

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.Asp482Val
Coding: c.1445A>T
MANE Select: NM_002299
dbSNP: rs2467231309
Type: single nucleotide variant
Location: chr2:135817603 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 482: the 'glycosyl hydrolase-1 2; region ii' region

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LCT p.Ala1398Glu Uncertain significance ★★ ⚠ same condition
LCT p.Ala148Gly Uncertain significance ★★ ⚠ same condition
LCT p.Ala158Val Uncertain significance ★★ ⚠ same condition
LCT p.Ala372Val Uncertain significance ★★ ⚠ same condition
LCT p.Ala424Val Uncertain significance ★★ ⚠ same condition
LCT p.Ala694Thr Uncertain significance ★★ ⚠ same condition
LCT p.Ala921Ser Uncertain significance ★★ ⚠ same condition
LCT p.Arg1198Gly 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-asp482val (accessed [today's date]).

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