Is LRAT p.Pro173= (c.519G>T) pathogenic?

LRAT p.Pro173= (c.519G>T) is classified Conflicting classifications of pathogenicity in LRAT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-04-21). Ultra-rare (popmax 0.0173%, afr); Associated with Leber congenital amaurosis 14.

What condition is associated with LRAT p.Pro173= (c.519G>T)?

LRAT p.Pro173= (c.519G>T) is associated with Leber congenital amaurosis 14, retinitis pigmentosa (ClinVar).

How common is LRAT p.Pro173= (c.519G>T) in the general population?

LRAT p.Pro173= (c.519G>T) is ultra-rare (popmax 0.0173%, afr) (gnomAD).

How is Leber congenital amaurosis inherited?

Typically Autosomal dominant, Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

LRAT p.Pro173=

c.519G>T · rs375365480 · VCV902419

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0173%, afr)

Conditions

Leber congenital amaurosis 14

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -3.5
Overall
CADD	1.837	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0173% African / African-American · 13/74,964 alleles

Filtering AF 0.0102% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00812%

Overall 0.00112% 18/1,613,412 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0173%	5,766
Remaining individualsnot grpmax-eligible	0.0032%	31,251
Admixed American	0.00167%	60,002
South Asian	0.0011%	91,058
European (non-Finnish)	8.47e-05%	1,179,948

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: LRAT
Protein: p.Pro173=
Coding: c.519G>T
MANE Select: NM_004744
dbSNP: rs375365480
Type: single nucleotide variant
Location: chr4:154744845 (GRCh38)
Gene constraint: LOEUF 1.214 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 83.69
Residue 173: the lrat domain; a UniProt-annotated variant site (in)

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

Disease context

Leber congenital amaurosis 14 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: retinitis pigmentosa

For Leber congenital amaurosis (Orphanet):

Inheritance: Autosomal dominant, Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: 1-9 / 100 000 (Europe)

Similar variants

LRAT p.Pro173Ser Uncertain significance ★★ ⚠ same residue
LRAT p.Pro173Leu Uncertain significance ★ ⚠ same residue
LRAT p.Arg47Ter Pathogenic/Likely pathogenic ★★ same condition
LRAT p.Arg55Trp Pathogenic ★★ same condition
LRAT p.Cys168Ter Pathogenic ★★ same condition
LRAT c.*2625A>G Uncertain significance ★★ same condition
LRAT p.Arg69Cys Uncertain significance ★★ ⚠ same condition
LRAT p.Asn159Ser 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/lrat-p-pro173 (accessed [today's date]).

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