Is LCAT p.Pro4= (c.12C>T) pathogenic?

LCAT p.Pro4= (c.12C>T) is classified Likely benign in LCAT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-21). Very rare (popmax 0.00358%, sas); Associated with Cardiovascular phenotype.

What condition is associated with LCAT p.Pro4= (c.12C>T)?

LCAT p.Pro4= (c.12C>T) is associated with Cardiovascular phenotype (ClinVar).

How common is LCAT p.Pro4= (c.12C>T) in the general population?

LCAT p.Pro4= (c.12C>T) is very rare (popmax 0.00358%, sas) (gnomAD).

LCAT p.Pro4=

c.12C>T · rs912256784 · VCV1769360

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00358%, sas)

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 -2.1
Overall
CADD	1.633	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00358% South Asian · 3/83,894 alleles

Filtering AF 0.00095% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000463%

Overall 0.000969% 15/1,547,676 alleles · very rare exomes 12/1,395,490 · genomes 3/152,186 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00358%	27,965
African / African-American	0.00274%	36,487
Remaining individualsnot grpmax-eligible	0.00167%	59,860
European (non-Finnish)	0.000785%	127,361

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.Pro4=
Coding: c.12C>T
MANE Select: NM_000229
dbSNP: rs912256784
Type: single nucleotide variant
Location: chr16:67944090 (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.Pro4Ser 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-pro4 (accessed [today's date]).

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