Is LIPC p.Cys75= (c.225C>T) pathogenic?

LIPC p.Cys75= (c.225C>T) is classified Likely benign in LIPC (ClinVar, Single submitter, 1 submitter; last evaluated 2021-04-06). Ultra-rare (popmax 0.033%, mid).

How common is LIPC p.Cys75= (c.225C>T) in the general population?

LIPC p.Cys75= (c.225C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

LIPC p.Cys75=

c.225C>T · rs146362585 · VCV1576792

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.38 · evaluated, not missing
Constraint at this position
Conservation	phyloP -6.1	GERP 0.17
Overall
CADD	6.927	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.033% Middle Eastern · 2/6,062 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00242%

Overall 0.00155% 25/1,614,144 alleles · ultra-rare exomes 23/1,461,860 · genomes 2/152,284 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,031
African / African-American	0.00666%	15,008
Remaining individualsnot grpmax-eligible	0.0048%	20,837
South Asian	0.0022%	45,544
European (non-Finnish)	0.0011%	90,769

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: LIPC
Protein: p.Cys75=
Coding: c.225C>T
MANE Select: NM_000236
dbSNP: rs146362585
Type: single nucleotide variant
Location: chr15:58538469 (GRCh38)
Gene constraint: LOEUF 1.102 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.03

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

Similar variants

LIPC p.Cys75Ter Uncertain significance ★ same residue
LIPC c.456+2T>C Uncertain significance ★★ same type
LIPC c.456+5C>T Uncertain significance ★★ same type
LIPC p.Ala105Val Uncertain significance ★★ ⚠ same type
LIPC p.Ala106Val Uncertain significance ★★ ⚠ same type
LIPC p.Arg135Cys Uncertain significance ★★ ⚠ same type
LIPC p.Arg135His Uncertain significance ★★ ⚠ same type
LIPC p.Arg138Cys 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/lipc-p-cys75 (accessed [today's date]).

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