Is CPLX4 p.Arg107Trp (c.319C>T) pathogenic?

CPLX4 p.Arg107Trp (c.319C>T) is classified Uncertain significance in CPLX4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-13). AlphaMissense: likely benign (0.2073); Ultra-rare (popmax 0.0134%, eas).

How common is CPLX4 p.Arg107Trp (c.319C>T) in the general population?

CPLX4 p.Arg107Trp (c.319C>T) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CPLX4 p.Arg107Trp (c.319C>T)?

AlphaMissense predicts likely benign (score 0.2073) — an in-silico prediction, not a clinical call.

CPLX4 p.Arg107Trp

c.319C>T · VCV3496415

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2073 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2073	likely benign
REVEL	0.249	benign-leaning
SaProt	LLR -11.84	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP -1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 22 kb · p 0.99 · regional, not allelic
Overall
CADD	24.5	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 0.0134% East Asian · 6/44,882 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00155% 25/1,613,292 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,480
African / African-American	0.00268%	37,377
Remaining individualsnot grpmax-eligible	0.0016%	62,470
European (non-Finnish)	0.00136%	73,747

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: CPLX4
Protein: p.Arg107Trp
Coding: c.319C>T
MANE Select: NM_181654
Type: single nucleotide variant
Location: chr18:59296862 (GRCh38)
Gene constraint: LOEUF 1.729 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 74.26

Full CPLX4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CPLX4 p.Ala153Thr Uncertain significance ★ ⚠ same type
CPLX4 p.Ala35Val Uncertain significance ★ ⚠ same type
CPLX4 p.Ala36Gly Uncertain significance ★ ⚠ same type
CPLX4 p.Ala62Ser Uncertain significance ★ ⚠ same type
CPLX4 p.Asp119Asn Uncertain significance ★ ⚠ same type
CPLX4 p.Asp60Glu Uncertain significance ★ ⚠ same type
CPLX4 p.Gln12Lys Uncertain significance ★ ⚠ same type
CPLX4 p.His76Leu 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/cplx4-p-arg107trp (accessed [today's date]).

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