Is LIPE p.Arg810Trp (c.2428C>T) pathogenic?

LIPE p.Arg810Trp (c.2428C>T) is classified Uncertain significance in LIPE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely benign (0.1647); Very rare (popmax 0.00167%, amr); Associated with Inborn genetic diseases.

What condition is associated with LIPE p.Arg810Trp (c.2428C>T)?

LIPE p.Arg810Trp (c.2428C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LIPE p.Arg810Trp (c.2428C>T) in the general population?

LIPE p.Arg810Trp (c.2428C>T) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about LIPE p.Arg810Trp (c.2428C>T)?

AlphaMissense predicts likely benign (score 0.1647) — an in-silico prediction, not a clinical call.

LIPE p.Arg810Trp

c.2428C>T · rs1314032334 · VCV3119048

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1647 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1647	likely benign
REVEL	0.105	moderately benign-leaning
SaProt	LLR -10.11	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.6	phastCons 0.78
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.019 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00167% Admixed American · 1/60,004 alleles

Filtering AF 0.000429% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000312%

Overall 0.000805% 13/1,614,030 alleles · very rare exomes 11/1,461,806 · genomes 2/152,224 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	60,004
African / African-American	0.00133%	74,944
South Asian	0.0011%	91,082
European (non-Finnish)	0.000847%	118,001

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: LIPE
Protein: p.Arg810Trp
Coding: c.2428C>T
MANE Select: NM_005357
dbSNP: rs1314032334
Type: single nucleotide variant
Location: chr19:42405499 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.77 · 1 PDB

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

LIPE p.Arg810Gln Uncertain significance ★ ⚠ same residue
LIPE p.Gln150Glu Uncertain significance ★★ ⚠ same condition
LIPE p.Leu777Phe Uncertain significance ★★ ⚠ same condition
LIPE p.Asn499= Likely benign ★★ same condition
LIPE p.Gly445= Likely benign ★★ same condition
LIPE p.Ala1055Ser Uncertain significance ★ ⚠ same condition
LIPE p.Ala159Thr Uncertain significance ★ ⚠ same condition
LIPE p.Ala345Val 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/lipe-p-arg810trp (accessed [today's date]).

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