Is LIPE p.Ala676Val (c.2027C>T) pathogenic?

LIPE p.Ala676Val (c.2027C>T) is classified Likely benign in LIPE (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-11). AlphaMissense: likely benign (0.0618); Rare (popmax 0.116%, eas); Associated with Inborn genetic diseases.

What condition is associated with LIPE p.Ala676Val (c.2027C>T)?

LIPE p.Ala676Val (c.2027C>T) is associated with Inborn genetic diseases (ClinVar).

How common is LIPE p.Ala676Val (c.2027C>T) in the general population?

LIPE p.Ala676Val (c.2027C>T) is rare (popmax 0.116%, eas) (gnomAD).

What do computational predictors say about LIPE p.Ala676Val (c.2027C>T)?

AlphaMissense predicts likely benign (score 0.0618) — an in-silico prediction, not a clinical call.

LIPE p.Ala676Val

c.2027C>T · rs765951365 · VCV2460536

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0618 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.116%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0618	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -3.22	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 1.6	phastCons 0.024
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.019 · regional, not allelic
Overall
CADD	4.725	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 0.116% East Asian · 52/44,702 alleles

Filtering AF 0.091% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0821%

Overall 0.00528% 85/1,608,640 alleles · rare exomes 70/1,456,402 · genomes 15/152,238 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.116%	860
Remaining individualsnot grpmax-eligible	0.0225%	4,446
South Asian	0.0199%	5,014
European (non-Finnish)	8.49e-05%	1,177,780

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.Ala676Val
Coding: c.2027C>T
MANE Select: NM_005357
dbSNP: rs765951365
Type: single nucleotide variant
Location: chr19:42407284 (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.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
LIPE p.Ala351Val 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-ala676val (accessed [today's date]).

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