Is CACTIN p.Arg301Gln (c.902G>A) pathogenic?

CACTIN p.Arg301Gln (c.902G>A) is classified Uncertain significance in CACTIN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). AlphaMissense: likely benign (0.1334); Very rare (popmax 0.00333%, amr).

How common is CACTIN p.Arg301Gln (c.902G>A) in the general population?

CACTIN p.Arg301Gln (c.902G>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CACTIN p.Arg301Gln (c.902G>A)?

AlphaMissense predicts likely benign (score 0.1334) — an in-silico prediction, not a clinical call.

CACTIN p.Arg301Gln

c.902G>A · VCV3484237

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1334 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1334	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -5.42	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 7.6	GERP -0.75, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 10 kb · p 2.8e-11 · regional, not allelic
Overall
CADD	23.9	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

Grpmax group 0.00333% Admixed American · 2/59,972 alleles

Filtering AF 0.000553% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.00105% 17/1,613,176 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,572
Admixed Americangrpmax	0.00333%	29,986
South Asian	0.0022%	45,511
African / African-American	0.00133%	74,952
European (non-Finnish)	0.000932%	107,250

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CACTIN
Protein: p.Arg301Gln
Coding: c.902G>A
MANE Select: NM_001080543
Type: single nucleotide variant
Location: chr19:3619225 (GRCh38)
Gene constraint: LOEUF 0.465 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.52 · 6 PDB

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

Similar variants

CACTIN p.Arg301Trp 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
CACTIN p.Ala500Val 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-arg301gln (accessed [today's date]).

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