Is LIPE p.Tyr428= (c.1284C>T) pathogenic?

LIPE p.Tyr428= (c.1284C>T) is classified Likely benign in LIPE (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-18). Very rare (popmax 0.00333%, amr).

How common is LIPE p.Tyr428= (c.1284C>T) in the general population?

LIPE p.Tyr428= (c.1284C>T) is very rare (popmax 0.00333%, amr) (gnomAD).

LIPE p.Tyr428=

c.1284C>T · VCV4942748

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

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 -9.1
Overall
CADD	0.717	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,034 alleles

Filtering AF 0.00196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00168%

Overall 0.0327% 528/1,614,160 alleles · very rare exomes 433/1,461,808 · genomes 95/152,352 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.742%	135
Remaining individualsnot grpmax-eligible	0.0256%	3,907
Admixed Americangrpmax	0.00333%	30,017
European (non-Finnish)	0.00271%	36,876
East Asian	0.00223%	44,880
African / African-American	0.00133%	75,064
South Asian	0.0011%	91,090

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Tyr428=
Coding: c.1284C>T
MANE Select: NM_005357
Type: single nucleotide variant
Location: chr19:42410442 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.77 · 1 PDB
Residue 428: an α-helix

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

Similar variants

LIPE p.Arg305Cys Uncertain significance ★★ ⚠ same type
LIPE p.Arg821Cys Uncertain significance ★★ ⚠ same type
LIPE p.Gln150Glu Uncertain significance ★★ ⚠ same type
LIPE p.Leu1027Met Uncertain significance ★★ ⚠ same type
LIPE p.Leu777Phe Uncertain significance ★★ ⚠ same type
LIPE p.Val1014Met Uncertain significance ★★ ⚠ same type
LIPE c.2365+181T>A Benign ★★ same type
LIPE c.2968-44C>G Benign ★★ 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/lipe-p-tyr428 (accessed [today's date]).

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