Is LCT p.Ala577Ser (c.1729G>T) pathogenic?

LCT p.Ala577Ser (c.1729G>T) is classified Uncertain significance in LCT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.1458); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LCT p.Ala577Ser (c.1729G>T)?

LCT p.Ala577Ser (c.1729G>T) is associated with Inborn genetic diseases (ClinVar).

How common is LCT p.Ala577Ser (c.1729G>T) in the general population?

LCT p.Ala577Ser (c.1729G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LCT p.Ala577Ser (c.1729G>T)?

AlphaMissense predicts likely benign (score 0.1458) — an in-silico prediction, not a clinical call.

LCT p.Ala577Ser

c.1729G>T · VCV4623577

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1458 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1458	likely benign
REVEL	0.198	benign-leaning
SaProt	LLR -9.27	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 3.3	GERP 0.88, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 5,037 bp · p 1.3e-10 · regional, not allelic
Overall
CADD	19.67	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.Ala577Ser
Coding: c.1729G>T
MANE Select: NM_002299
Type: single nucleotide variant
Location: chr2:135812935 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 577: 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

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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-ala577ser (accessed [today's date]).

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