Is LCAT p.Pro7= (c.21A>G) pathogenic?

LCAT p.Pro7= (c.21A>G) is classified Likely benign in LCAT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-27). Very rare (popmax 0.00148%, nfe); Associated with Cardiovascular phenotype.

What condition is associated with LCAT p.Pro7= (c.21A>G)?

LCAT p.Pro7= (c.21A>G) is associated with Cardiovascular phenotype (ClinVar).

How common is LCAT p.Pro7= (c.21A>G) in the general population?

LCAT p.Pro7= (c.21A>G) is very rare (popmax 0.00148%, nfe) (gnomAD).

LCAT p.Pro7=

c.21A>G · VCV3537467

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00148%, 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 -0.7	phastCons 0.003
Overall
CADD	6.543	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00148% European (non-Finnish) · 17/1,146,316 alleles

Filtering AF 0.000903% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000739%

Overall 0.0011% 17/1,547,946 alleles · very rare exomes 17/1,395,740 · genomes 0/152,206 · 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.Pro7=
Coding: c.21A>G
MANE Select: NM_000229
Type: single nucleotide variant
Location: chr16:67944081 (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-pro7 (accessed [today's date]).

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