Is CACTIN p.Gln488Arg (c.1463A>G) pathogenic?

CACTIN p.Gln488Arg (c.1463A>G) is classified Uncertain significance in CACTIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-25). AlphaMissense: likely benign (0.0676); Absent from gnomAD v4.1.

How common is CACTIN p.Gln488Arg (c.1463A>G) in the general population?

CACTIN p.Gln488Arg (c.1463A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CACTIN p.Gln488Arg (c.1463A>G)?

AlphaMissense predicts likely benign (score 0.0676) — an in-silico prediction, not a clinical call.

CACTIN p.Gln488Arg

c.1463A>G · VCV3826797

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0676 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,580,934)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0676	likely benign
REVEL	0.02	moderately benign-leaning
SaProt	LLR -5.11	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 0.12	GERP -3.6, phastCons 0.01
Regional constraint	o/e 1.01	unconstrained · MANE · 1,214 bp · p 0.84 · regional, not allelic
Overall
CADD	9.286	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

No allele count reported in gnomAD v4.1 (AN 1,580,934). 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: CACTIN
Protein: p.Gln488Arg
Coding: c.1463A>G
MANE Select: NM_001080543
Type: single nucleotide variant
Location: chr19:3613479 (GRCh38)
Gene constraint: LOEUF 0.465 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.52 · 6 PDB
Residue 488: the 'disordered' region

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

Similar variants

CACTIN p.Gln488His Uncertain significance ★ ⚠ same residue
CACTIN p.Gln488Leu Uncertain significance ★ ⚠ same residue
CACTIN p.Ala100Ser Uncertain significance ★ ⚠ same type
CACTIN p.Ala119Val Uncertain significance ★ ⚠ same type
CACTIN p.Ala130Ser Uncertain significance ★ ⚠ same type
CACTIN p.Ala131Val Uncertain significance ★ ⚠ same type
CACTIN p.Ala317Thr Uncertain significance ★ ⚠ same type
CACTIN p.Ala427Thr 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/cactin-p-gln488arg (accessed [today's date]).

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