Is LCAT p.Pro437= (c.1311G>A) pathogenic?

LCAT p.Pro437= (c.1311G>A) is classified Likely benign in LCAT (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-06). Very rare (popmax 0.000933%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LCAT p.Pro437= (c.1311G>A)?

LCAT p.Pro437= (c.1311G>A) is associated with Cardiovascular phenotype (ClinVar).

How common is LCAT p.Pro437= (c.1311G>A) in the general population?

LCAT p.Pro437= (c.1311G>A) is very rare (popmax 0.000933%, nfe) (gnomAD).

LCAT p.Pro437=

c.1311G>A · VCV3290242

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000933%, 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 -2.4
Overall
CADD	4.109	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000933% European (non-Finnish) · 11/1,179,368 alleles

Filtering AF 0.000501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.000682% 11/1,612,402 alleles · very rare exomes 8/1,460,248 · genomes 3/152,154 · joint denominator

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.Pro437=
Coding: c.1311G>A
MANE Select: NM_000229
Type: single nucleotide variant
Location: chr16:67939916 (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.Pro437Leu Conflicting classifications of pathogenicity ★ ⚠ 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-pro437 (accessed [today's date]).

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