Is CPLX1 p.Pro127Gln (c.380C>A) pathogenic?

CPLX1 p.Pro127Gln (c.380C>A) is classified Uncertain significance in CPLX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-12-06). AlphaMissense: ambiguous (0.4535); Absent from gnomAD v4.1.

How common is CPLX1 p.Pro127Gln (c.380C>A) in the general population?

CPLX1 p.Pro127Gln (c.380C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CPLX1 p.Pro127Gln (c.380C>A)?

AlphaMissense predicts ambiguous (score 0.4535) — an in-silico prediction, not a clinical call.

CPLX1 p.Pro127Gln

c.380C>A · rs778428028 · VCV2069940

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4535 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,601,066)

Computational evidence

Protein change
AlphaMissense	0.4535	ambiguous
REVEL	0.323	indeterminate
SaProt	LLR -8.60	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 0.35, phastCons 1
Regional constraint	o/e 1.28	unconstrained · MANE · 38 kb · p 0.0001 · regional, not allelic
Overall
CADD	29.8	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

No allele count reported in gnomAD v4.1 (AN 1,601,066). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CPLX1
Protein: p.Pro127Gln
Coding: c.380C>A
MANE Select: NM_006651
dbSNP: rs778428028
Type: single nucleotide variant
Location: chr4:786526 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI 0.44 (gnomAD)
Structure: AlphaFold pLDDT 72.31 · 2 PDB
Residue 127: a UniProt-annotated variant site (in dee63)

Full CPLX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPLX1 p.Cys105Ter Pathogenic/Likely pathogenic ★★ same type
CPLX1 p.Glu108Ter Likely pathogenic ★★ same type
CPLX1 p.Asp113Glu Uncertain significance ★★ ⚠ same type
CPLX1 p.Asp29Ala Uncertain significance ★★ ⚠ same type
CPLX1 p.Gly104Asp Uncertain significance ★★ ⚠ same type
CPLX1 p.Lys75Glu Uncertain significance ★★ ⚠ same type
CPLX1 p.Tyr70Ter Uncertain significance ★★ same type
CPLX1 p.Val109Ala 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/cplx1-p-pro127gln (accessed [today's date]).

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