Is LCAT p.Pro293= (c.879C>T) pathogenic?

LCAT p.Pro293= (c.879C>T) is classified Conflicting classifications of pathogenicity in LCAT (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-01-27). Ultra-rare (popmax 0.0189%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LCAT p.Pro293= (c.879C>T)?

LCAT p.Pro293= (c.879C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is LCAT p.Pro293= (c.879C>T) in the general population?

LCAT p.Pro293= (c.879C>T) is ultra-rare (popmax 0.0189%, nfe) (gnomAD).

LCAT p.Pro293=

c.879C>T · rs200225997 · VCV1284301

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 0.0189%, nfe)

Conditions

Cardiovascular phenotype

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 0.57	phastCons 0.81
Overall
CADD	11.59	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0189% European (non-Finnish) · 223/1,180,048 alleles

Filtering AF 0.0168% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0161%

Overall 0.0148% 239/1,614,076 alleles · ultra-rare exomes 224/1,461,846 · genomes 15/152,230 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0189%	5,292
Finnishnot grpmax-eligible	0.0109%	9,144
Admixed American	0.005%	20,001
African / African-American	0.004%	24,983
Remaining individualsnot grpmax-eligible	0.0032%	31,243
East Asian	0.00223%	44,890

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: LCAT
Protein: p.Pro293=
Coding: c.879C>T
MANE Select: NM_000229
dbSNP: rs200225997
Type: single nucleotide variant
Location: chr16:67940348 (GRCh38)
Gene constraint: LOEUF 0.568 · pLI 0.77 (gnomAD)
Structure: AlphaFold pLDDT 87.33 · 7 PDB

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

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LCAT p.Arg423Cys Likely pathogenic ★★ ⚠ same condition
LCAT p.Ala432Thr Uncertain significance ★★ ⚠ same condition
LCAT p.Asp352Asn Uncertain significance ★★ ⚠ same condition
LCAT p.Gly128Ser Uncertain significance ★★ ⚠ same condition
LCAT p.Gly196Arg Uncertain significance ★★ ⚠ same condition
LCAT p.Gly398Arg Uncertain significance ★★ ⚠ same condition
LCAT p.Gly5Ser Uncertain significance ★★ ⚠ same condition
LCAT p.Leu309Val 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/lcat-p-pro293 (accessed [today's date]).

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