Is LRAT p.Pro173Ser (c.517C>T) pathogenic?

LRAT p.Pro173Ser (c.517C>T) is classified Uncertain significance in LRAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-17). AlphaMissense: likely benign (0.1128); Very rare (popmax 0.00267%, afr); Associated with Inborn genetic diseases.

What condition is associated with LRAT p.Pro173Ser (c.517C>T)?

LRAT p.Pro173Ser (c.517C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LRAT p.Pro173Ser (c.517C>T) in the general population?

LRAT p.Pro173Ser (c.517C>T) is very rare (popmax 0.00267%, afr) (gnomAD).

What do computational predictors say about LRAT p.Pro173Ser (c.517C>T)?

AlphaMissense predicts likely benign (score 0.1128) — an in-silico prediction, not a clinical call.

LRAT p.Pro173Ser

c.517C>T · rs145355018 · VCV839771

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1128 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00267%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1128	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -5.32	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 0.2
Regional constraint	o/e 0.94	unconstrained · MANE · 4,806 bp · p 0.28 · regional, not allelic
Overall
CADD	10.68	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 0.00267% African / African-American · 2/74,874 alleles

Filtering AF 0.000953% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000787%

Overall 0.0013% 21/1,613,480 alleles · very rare exomes 16/1,461,478 · genomes 5/152,002 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00267%	37,437
Remaining individualsnot grpmax-eligible	0.0016%	62,482
European (non-Finnish)	0.00153%	65,556

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.Pro173Ser
Coding: c.517C>T
MANE Select: NM_004744
dbSNP: rs145355018
Type: single nucleotide variant
Location: chr4:154744843 (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

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LRAT p.Pro173= Conflicting classifications of pathogenicity ★ same residue
LRAT p.Pro173Leu Uncertain significance ★ ⚠ same residue
LRAT p.Ala120Gly Uncertain significance ★★ ⚠ same condition
LRAT p.Gly210Arg Uncertain significance ★★ same condition
LRAT p.Ser27Trp Uncertain significance ★★ ⚠ same condition
LRAT p.Val105Glu Uncertain significance ★★ ⚠ same condition
LRAT p.Arg143Trp Uncertain significance ★ ⚠ same condition
LRAT p.Arg87Ser 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-pro173ser (accessed [today's date]).

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