Is ACIN1 p.Arg1237Gly (c.3709A>G) pathogenic?

ACIN1 p.Arg1237Gly (c.3709A>G) is classified Uncertain significance in ACIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-13). AlphaMissense: ambiguous (0.4724); Very rare (popmax 0.000171%, nfe).

How common is ACIN1 p.Arg1237Gly (c.3709A>G) in the general population?

ACIN1 p.Arg1237Gly (c.3709A>G) is very rare (popmax 0.000171%, nfe) (gnomAD).

What do computational predictors say about ACIN1 p.Arg1237Gly (c.3709A>G)?

AlphaMissense predicts ambiguous (score 0.4724) — an in-silico prediction, not a clinical call.

ACIN1 p.Arg1237Gly

c.3709A>G · rs1020804534 · VCV2255317

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4724 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000171%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4724	ambiguous
REVEL	0.053	moderately benign-leaning
SaProt	LLR -11.79	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.3	GERP -2.8, phastCons 0.037
Regional constraint	o/e 0.71	unconstrained · MANE · 10 kb · p 4.1e-15 · regional, not allelic
Overall
CADD	18.24	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R1295G vs ClinVar R1237G) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000171% European (non-Finnish) · 2/1,167,330 alleles

Filtering AF 2.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000138% 2/1,448,052 alleles · very rare

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: ACIN1
Protein: p.Arg1237Gly
Coding: c.3709A>G
MANE Select: NM_001386863
dbSNP: rs1020804534
Type: single nucleotide variant
Location: chr14:23059291 (GRCh38)
Gene constraint: LOEUF 0.15 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.21 · 1 PDB
Residue 1237: the 'disordered' region; the 'sufficient for interaction with rnps1 and sap18 and formation of the asap complex' region

Full ACIN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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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/acin1-p-arg1237gly (accessed [today's date]).

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