Is LCT p.Gln95Pro (c.284A>C) pathogenic?

LCT p.Gln95Pro (c.284A>C) is classified Uncertain significance in LCT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-07). AlphaMissense: likely benign (0.2321); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with LCT p.Gln95Pro (c.284A>C)?

LCT p.Gln95Pro (c.284A>C) is associated with Inborn genetic diseases (ClinVar).

How common is LCT p.Gln95Pro (c.284A>C) in the general population?

LCT p.Gln95Pro (c.284A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LCT p.Gln95Pro (c.284A>C)?

AlphaMissense predicts likely benign (score 0.2321) — an in-silico prediction, not a clinical call.

LCT p.Gln95Pro

c.284A>C · VCV4046637

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2321 · 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	0.2321	likely benign
REVEL	0.225	benign-leaning
SaProt	LLR -9.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.63	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 0.063	GERP -0.85, phastCons 0.01
Regional constraint	o/e 0.89	unconstrained · MANE · 19 kb · p 0.02 · regional, not allelic
Overall
CADD	18.77	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.Gln95Pro
Coding: c.284A>C
MANE Select: NM_002299
Type: single nucleotide variant
Location: chr2:135836886 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 86.63
Residue 95: the 'glycosyl hydrolase-1 1; region i' 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-gln95pro (accessed [today's date]).

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