Is CPLX1 p.Pro103Leu (c.308C>T) pathogenic?

CPLX1 p.Pro103Leu (c.308C>T) is classified Likely benign in CPLX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-26). AlphaMissense: likely benign (0.114); Rare (popmax 0.19%, eas).

How common is CPLX1 p.Pro103Leu (c.308C>T) in the general population?

CPLX1 p.Pro103Leu (c.308C>T) is rare (popmax 0.19%, eas) (gnomAD).

What do computational predictors say about CPLX1 p.Pro103Leu (c.308C>T)?

AlphaMissense predicts likely benign (score 0.114) — an in-silico prediction, not a clinical call.

CPLX1 p.Pro103Leu

c.308C>T · rs574433619 · VCV736367

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.114 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.19%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.114	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -8.75	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 11	GERP 1.4, phastCons 1
Regional constraint	o/e 1.28	unconstrained · MANE · 38 kb · p 0.0001 · regional, not allelic
Overall
CADD	26.3	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 0.19% East Asian · 85/44,788 alleles

Filtering AF 0.157% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.145%

Overall 0.00664% 107/1,612,252 alleles · rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.19%	527
South Asian	0.00991%	10,096
Remaining individualsnot grpmax-eligible	0.00801%	12,479
Admixed American	0.00167%	59,934
European (non-Finnish)	0.000594%	168,478

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: CPLX1
Protein: p.Pro103Leu
Coding: c.308C>T
MANE Select: NM_006651
dbSNP: rs574433619
Type: single nucleotide variant
Location: chr4:786598 (GRCh38)
Gene constraint: LOEUF 0.756 · pLI 0.44 (gnomAD)
Structure: AlphaFold pLDDT 72.31 · 2 PDB
Residue 103: the 'disordered' region

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

Similar variants

CPLX1 p.Pro103= Likely benign ★ same residue
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

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-pro103leu (accessed [today's date]).

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