Is LIPE p.Glu174= (c.522A>G) pathogenic?

LIPE p.Glu174= (c.522A>G) is classified Benign/Likely benign in LIPE (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-05-28). Rare (popmax 0.372%, afr).

How common is LIPE p.Glu174= (c.522A>G) in the general population?

LIPE p.Glu174= (c.522A>G) is rare (popmax 0.372%, afr) (gnomAD).

LIPE p.Glu174=

c.522A>G · rs149105201 · VCV742549

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.372%, afr)

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 0.58
Overall
CADD	1.406	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.372% African / African-American · 279/75,050 alleles

Filtering AF 0.336% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.322%

Overall 0.0186% 301/1,614,214 alleles · rare exomes 128/1,461,892 · genomes 173/152,322 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.372%	269
Admixed American	0.015%	6,668
Remaining individualsnot grpmax-eligible	0.0144%	6,945
European (non-Finnish)	0.000339%	295,012

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.Glu174=
Coding: c.522A>G
MANE Select: NM_005357
dbSNP: rs149105201
Type: single nucleotide variant
Location: chr19:42426628 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.77 · 1 PDB
Residue 174: the 'disordered' region

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

Similar variants

LIPE p.Glu174Gln Uncertain significance ★ ⚠ same residue
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

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-glu174 (accessed [today's date]).

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