Is ACIN1 p.Arg142Ser (c.426A>C) pathogenic?

ACIN1 p.Arg142Ser (c.426A>C) is classified Uncertain significance in ACIN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-03). AlphaMissense: ambiguous (0.4837); Very rare (popmax 0.00134%, afr).

How common is ACIN1 p.Arg142Ser (c.426A>C) in the general population?

ACIN1 p.Arg142Ser (c.426A>C) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ACIN1 p.Arg142Ser (c.426A>C)?

AlphaMissense predicts ambiguous (score 0.4837) — an in-silico prediction, not a clinical call.

ACIN1 p.Arg142Ser

c.426A>C · VCV3480865

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4837 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4837	ambiguous
REVEL	0.08	moderately benign-leaning
SaProt	LLR -4.97	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 5.7, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 21 kb · p 0.37 · regional, not allelic
Overall
CADD	23.5	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 R200S vs ClinVar R142S) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00134% African / African-American · 1/74,896 alleles

Overall 0.000657% 1/152,228 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.Arg142Ser
Coding: c.426A>C
MANE Select: NM_001386863
Type: single nucleotide variant
Location: chr14:23089992 (GRCh38)
Gene constraint: LOEUF 0.15 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 51.21 · 1 PDB

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

Similar variants

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ACIN1 p.Ala39Thr Uncertain significance ★ ⚠ same type
ACIN1 p.Ala502Val Uncertain significance ★ ⚠ same type
ACIN1 p.Ala557Val Uncertain significance ★ ⚠ same type
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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-arg142ser (accessed [today's date]).

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