Is LCAT p.Pro48= (c.144C>T) pathogenic?

LCAT p.Pro48= (c.144C>T) is classified Likely benign in LCAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-26). Ultra-rare (popmax 0.0416%, eas); Associated with Cardiovascular phenotype.

What condition is associated with LCAT p.Pro48= (c.144C>T)?

LCAT p.Pro48= (c.144C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is LCAT p.Pro48= (c.144C>T) in the general population?

LCAT p.Pro48= (c.144C>T) is ultra-rare (popmax 0.0416%, eas) (gnomAD).

LCAT p.Pro48=

c.144C>T · rs1181298236 · VCV3018303

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0416%, eas)

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 -0.4	phastCons 0.002
Overall
CADD	6.119	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0416% East Asian · 17/40,862 alleles

Filtering AF 0.0264% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0217%

Overall 0.002% 31/1,546,898 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0416%	2,404
Remaining individualsnot grpmax-eligible	0.00167%	59,854
European (non-Finnish)	0.00114%	88,055

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.Pro48=
Coding: c.144C>T
MANE Select: NM_000229
dbSNP: rs1181298236
Type: single nucleotide variant
Location: chr16:67943958 (GRCh38)
Gene constraint: LOEUF 0.568 · pLI 0.77 (gnomAD)
Structure: AlphaFold pLDDT 87.33 · 7 PDB
Residue 48: an α-helix

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.Pro48Leu Uncertain significance ★ ⚠ same residue
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

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-pro48 (accessed [today's date]).

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