Is LIPE p.Ser888Pro (c.2662T>C) pathogenic?

LIPE p.Ser888Pro (c.2662T>C) is classified Benign in LIPE (ClinVar, Single submitter, 2 submitters; last evaluated 2018-12-26). AlphaMissense: likely benign (0.0726); Low-frequency (popmax 2.8%, eas).

How common is LIPE p.Ser888Pro (c.2662T>C) in the general population?

LIPE p.Ser888Pro (c.2662T>C) is low-frequency (popmax 2.8%, eas) (gnomAD).

What do computational predictors say about LIPE p.Ser888Pro (c.2662T>C)?

AlphaMissense predicts likely benign (score 0.0726) — an in-silico prediction, not a clinical call.

LIPE p.Ser888Pro

c.2662T>C · rs70937099 · VCV708271

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0726 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 2.8%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0726	likely benign
REVEL	0.005	strongly benign-leaning
SaProt	LLR -6.39	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 0.38	phastCons 0.011
Regional constraint	o/e 0.94	unconstrained · MANE · 25 kb · p 0.019 · regional, not allelic
Overall
CADD	4.594	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 2.8% East Asian · 1,257/44,848 alleles

Filtering AF 2.67% ClinGen BA1/BS1 input FAF95, joint · FAF99 2.62%

Overall 0.0861% 1,388/1,611,958 alleles · low-frequency exomes 1,192/1,460,250 · genomes 196/151,708 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	2.8%	36
Remaining individualsnot grpmax-eligible	0.118%	844
South Asian	0.0297%	3,371
African / African-American	0.0214%	4,675
Admixed American	0.0133%	7,497
European (non-Finnish)	0.000509%	196,641

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.Ser888Pro
Coding: c.2662T>C
MANE Select: NM_005357
dbSNP: rs70937099
Type: single nucleotide variant
Location: chr19:42402912 (GRCh38)
Gene constraint: LOEUF 0.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.77 · 1 PDB
Residue 888: the 'disordered' region

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-ser888pro (accessed [today's date]).

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