Is LPCAT3 p.Val18Phe (c.52G>T) pathogenic?

LPCAT3 p.Val18Phe (c.52G>T) is classified Uncertain significance in LPCAT3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-14). AlphaMissense: likely benign (0.0663); Very rare (popmax 0.00687%, nfe).

How common is LPCAT3 p.Val18Phe (c.52G>T) in the general population?

LPCAT3 p.Val18Phe (c.52G>T) is very rare (popmax 0.00687%, nfe) (gnomAD).

What do computational predictors say about LPCAT3 p.Val18Phe (c.52G>T)?

AlphaMissense predicts likely benign (score 0.0663) — an in-silico prediction, not a clinical call.

LPCAT3 p.Val18Phe

c.52G>T · rs782445575 · VCV2361203

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0663 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00687%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0663	likely benign
REVEL	0.157	moderately benign-leaning
SaProt	LLR -6.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.5	GERP 0.46, phastCons 0.99
Regional constraint	o/e 0.87	unconstrained · MANE · 37 kb · p 0.12 · regional, not allelic
Overall
CADD	10.26	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00687% European (non-Finnish) · 81/1,179,238 alleles

Filtering AF 0.00563% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.00502% 81/1,612,240 alleles · very rare exomes 79/1,460,026 · genomes 2/152,214 · 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: LPCAT3
Protein: p.Val18Phe
Coding: c.52G>T
MANE Select: NM_005768
dbSNP: rs782445575
Type: single nucleotide variant
Location: chr12:7018373 (GRCh38)
Gene constraint: LOEUF 0.485 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 92.53

Full LPCAT3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LPCAT3 p.Val18Leu Uncertain significance ★ ⚠ same residue
LPCAT3 p.Ala5Thr Uncertain significance ★ ⚠ same type
LPCAT3 p.Gln24Pro Uncertain significance ★ ⚠ same type
LPCAT3 p.Glu25Gly Uncertain significance ★ ⚠ same type
LPCAT3 p.Leu15Pro Uncertain significance ★ ⚠ same type
LPCAT3 p.Leu72Phe Uncertain significance ★ ⚠ same type
LPCAT3 p.Ser4Leu Uncertain significance ★ ⚠ same type

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/lpcat3-p-val18phe (accessed [today's date]).

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