Is CPLX2 p.Leu117Pro (c.350T>C) pathogenic?

CPLX2 p.Leu117Pro (c.350T>C) is classified Uncertain significance in CPLX2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-27). AlphaMissense: likely pathogenic (0.9873); Very rare (popmax 0.00891%, eas).

How common is CPLX2 p.Leu117Pro (c.350T>C) in the general population?

CPLX2 p.Leu117Pro (c.350T>C) is very rare (popmax 0.00891%, eas) (gnomAD).

What do computational predictors say about CPLX2 p.Leu117Pro (c.350T>C)?

AlphaMissense predicts likely pathogenic (score 0.9873) — an in-silico prediction, not a clinical call.

CPLX2 p.Leu117Pro

c.350T>C · rs768201279 · VCV3076718

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9873 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00891%, eas)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9873	likely pathogenic
REVEL	0.669	pathogenic-leaning
SaProt	LLR -13.26	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.8	GERP 1.6, phastCons 1
Regional constraint	o/e 0.79	unconstrained · MANE · 1,302 bp · p 0.0055 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.00891% East Asian · 4/44,896 alleles

Filtering AF 0.00298% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0018%

Overall 0.000248% 4/1,613,918 alleles · very rare

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: CPLX2
Protein: p.Leu117Pro
Coding: c.350T>C
MANE Select: NM_001008220
dbSNP: rs768201279
Type: single nucleotide variant
Location: chr5:175879990 (GRCh38)
Gene constraint: LOEUF 0.683 · pLI 0.70 (gnomAD)
Structure: AlphaFold pLDDT 71.01

Full CPLX2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPLX2 p.Ala103Val Uncertain significance ★ ⚠ same type
CPLX2 p.Arg42Gln Uncertain significance ★ ⚠ same type
CPLX2 p.Glu58Gly Uncertain significance ★ ⚠ same type
CPLX2 p.Gly126Arg Uncertain significance ★ ⚠ same type
CPLX2 p.Gly21Glu Uncertain significance ★ ⚠ same type
CPLX2 p.Lys134Glu Uncertain significance ★ ⚠ same type
CPLX2 p.Pro102Ser 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/cplx2-p-leu117pro (accessed [today's date]).

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