Is LCP2 p.Val188= (c.564G>A) pathogenic?

LCP2 p.Val188= (c.564G>A) is classified Benign in LCP2 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-21). Common (popmax 59.8%, eas) — too common for a highly-penetrant pathogenic allele.

LCP2 p.Val188=

Q: How common is LCP2 p.Val188= (c.564G>A) in the general population?

LCP2 p.Val188= (c.564G>A) is common (popmax 59.8%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.564G>A · rs2292254 · VCV2688279

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Common

common (popmax 59.8%, eas) — too common for a highly-penetrant pathogenic allele

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 1.1	GERP 0.75, phastCons 1
Overall
CADD	7.214	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 59.8% East Asian · 6,279/10,496 alleles

Filtering AF 58.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 58.1%

Overall 36.8% 143,187/389,238 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	59.9%	2
East Asiangrpmax	59.8%	2
Admixed American	45.9%	2
South Asian	38.6%	3
Finnishnot grpmax-eligible	38.4%	3
European (non-Finnish)	36.6%	3
Remaining individualsnot grpmax-eligible	32.6%	3
African / African-American	30.7%	3
Ashkenazi Jewishnot grpmax-eligible	27.1%	4
Middle Eastern	26.3%	4

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: LCP2
Protein: p.Val188=
Coding: c.564G>A
MANE Select: NM_005565
dbSNP: rs2292254
Type: single nucleotide variant
Location: chr5:170268442 (GRCh38)
Gene constraint: LOEUF 0.465 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 63.50 · 5 PDB
Residue 188: an α-helix; the 'disordered' region

Full LCP2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

LCP2 p.Arg407Trp Uncertain significance ★★ ⚠ same type
LCP2 p.Pro328Leu Uncertain significance ★★ ⚠ same type
LCP2 c.142-18T>C Benign ★★ same type
LCP2 c.523+16C>T Benign ★★ same type
LCP2 p.Gln326= Benign ★★ same type
LCP2 p.Pro242= Benign ★★ same type
LCP2 p.Ser410Cys Benign/Likely benign ★★ same type
LCP2 p.Ala143Thr 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/lcp2-p-val188 (accessed [today's date]).

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