Is LCT p.Ala798Val (c.2393C>T) pathogenic?

LCT p.Ala798Val (c.2393C>T) is classified Uncertain significance in LCT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-06). AlphaMissense: likely benign (0.0891); Very rare (popmax 8.48e-05%, nfe).

How common is LCT p.Ala798Val (c.2393C>T) in the general population?

LCT p.Ala798Val (c.2393C>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about LCT p.Ala798Val (c.2393C>T)?

AlphaMissense predicts likely benign (score 0.0891) — an in-silico prediction, not a clinical call.

LCT p.Ala798Val

c.2393C>T · rs536149502 · VCV1470065

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0891 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0891	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -6.84	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 0.55	GERP -2, phastCons 0.033
Regional constraint	o/e 0.82	unconstrained · MANE · 5,551 bp · p 1.8e-08 · regional, not allelic
Overall
CADD	11.35	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

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,870 alleles

Overall 6.2e-05% 1/1,613,988 alleles · very rare exomes 0/1,461,646 · genomes 1/152,342 · joint denominator

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.Ala798Val
Coding: c.2393C>T
MANE Select: NM_002299
dbSNP: rs536149502
Type: single nucleotide variant
Location: chr2:135809954 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 798: the 'glycosyl hydrolase-1 2; region ii' region

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

Similar variants

LCT p.Ala798= 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
LCT p.Ala1398Glu Uncertain significance ★★ ⚠ same type
LCT p.Ala1483Thr 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-ala798val (accessed [today's date]).

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