Is LIPC p.Asp2Val (c.5A>T) pathogenic?

LIPC p.Asp2Val (c.5A>T) is classified Uncertain significance in LIPC (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-01). AlphaMissense: likely benign (0.1059); Ultra-rare (popmax 0.0165%, mid).

How common is LIPC p.Asp2Val (c.5A>T) in the general population?

LIPC p.Asp2Val (c.5A>T) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about LIPC p.Asp2Val (c.5A>T)?

AlphaMissense predicts likely benign (score 0.1059) — an in-silico prediction, not a clinical call.

LIPC p.Asp2Val

c.5A>T · rs756402865 · VCV2985171

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1059 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1059	likely benign
REVEL	0.284	benign-leaning
SaProt	LLR -6.08	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	GERP -3.2, phastCons 0.91
Regional constraint	o/e 1.08	unconstrained · MANE · 137 kb · p 0.056 · regional, not allelic
Overall
CADD	13.58	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 0.0165% Middle Eastern · 1/6,078 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.0013% 21/1,613,216 alleles · ultra-rare exomes 19/1,461,016 · genomes 2/152,200 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,078
South Asian	0.00769%	13,009
Remaining individualsnot grpmax-eligible	0.0016%	62,438
European (non-Finnish)	0.00102%	98,274

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.Asp2Val
Coding: c.5A>T
MANE Select: NM_000236
dbSNP: rs756402865
Type: single nucleotide variant
Location: chr15:58432037 (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 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
LIPC p.Arg225Gln 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-asp2val (accessed [today's date]).

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