Is CACTIN p.Arg107His (c.320G>A) pathogenic?

CACTIN p.Arg107His (c.320G>A) is classified Uncertain significance in CACTIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-08). AlphaMissense: likely benign (0.0771); Very rare (popmax 0.00223%, eas).

How common is CACTIN p.Arg107His (c.320G>A) in the general population?

CACTIN p.Arg107His (c.320G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about CACTIN p.Arg107His (c.320G>A)?

AlphaMissense predicts likely benign (score 0.0771) — an in-silico prediction, not a clinical call.

CACTIN p.Arg107His

c.320G>A · VCV3826794

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0771	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -8.80	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 -0.81	GERP -1.1, phastCons 0.001
Regional constraint	o/e 1.07	unconstrained · MANE · 2,909 bp · p 0.27 · regional, not allelic
Overall
CADD	7.648	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 0.00223% East Asian · 1/44,852 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000482% 7/1,453,114 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,852
Admixed American	0.00167%	59,944
Remaining individualsnot grpmax-eligible	0.0016%	62,382
European (non-Finnish)	0.000339%	294,863

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.Arg107His
Coding: c.320G>A
MANE Select: NM_001080543
Type: single nucleotide variant
Location: chr19:3624010 (GRCh38)
Gene constraint: LOEUF 0.465 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 69.52 · 6 PDB
Residue 107: the 'disordered' region

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

Similar variants

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
CACTIN p.Arg102Gln 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-arg107his (accessed [today's date]).

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