Is LRAT p.Asp33Glu (c.99C>A) pathogenic?

LRAT p.Asp33Glu (c.99C>A) is classified Uncertain significance in LRAT (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-30). AlphaMissense: likely benign (0.0769); Absent from gnomAD v4.1.

How common is LRAT p.Asp33Glu (c.99C>A) in the general population?

LRAT p.Asp33Glu (c.99C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about LRAT p.Asp33Glu (c.99C>A)?

AlphaMissense predicts likely benign (score 0.0769) — an in-silico prediction, not a clinical call.

LRAT p.Asp33Glu

c.99C>A · rs1732834528 · VCV961046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0769 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0769	likely benign
REVEL	0.091	moderately benign-leaning
SaProt	LLR -5.07	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 -0.05	GERP -0.77
Regional constraint	o/e 0.94	unconstrained · MANE · 4,806 bp · p 0.28 · regional, not allelic
Overall
CADD	11.95	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: LRAT
Protein: p.Asp33Glu
Coding: c.99C>A
MANE Select: NM_004744
dbSNP: rs1732834528
Type: single nucleotide variant
Location: chr4:154744425 (GRCh38)
Gene constraint: LOEUF 1.214 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.69

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

Similar variants

LRAT p.Asp33Asn Uncertain significance ★ ⚠ same residue
LRAT p.Asp33fs Pathogenic/Likely pathogenic ★★ same residue
LRAT p.Arg47Ter Pathogenic/Likely pathogenic ★★ same type
LRAT p.Arg55Gly Pathogenic/Likely pathogenic ★★ same type
LRAT p.Arg55Trp Pathogenic ★★ same type
LRAT p.Cys168Ter Pathogenic ★★ same type
LRAT p.Leu157Pro Likely pathogenic ★★ same type
LRAT c.*2625A>G 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/lrat-p-asp33glu (accessed [today's date]).

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