Is ARB2A p.Ala283Val (c.848C>T) pathogenic?

ARB2A p.Ala283Val (c.848C>T) is classified Uncertain significance in ARB2A (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-15). AlphaMissense: likely benign (0.1028); Ultra-rare (popmax 0.0437%, eas).

How common is ARB2A p.Ala283Val (c.848C>T) in the general population?

ARB2A p.Ala283Val (c.848C>T) is ultra-rare (popmax 0.0437%, eas) (gnomAD).

What do computational predictors say about ARB2A p.Ala283Val (c.848C>T)?

AlphaMissense predicts likely benign (score 0.1028) — an in-silico prediction, not a clinical call.

ARB2A p.Ala283Val

c.848C>T · rs767399233 · VCV2468413

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1028 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0437%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1028	likely benign
REVEL	0.1	moderately benign-leaning
SaProt	LLR -5.25	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 2.9, phastCons 1
Regional constraint	o/e 0.98	unconstrained · MANE · 454 kb · p 0.66 · regional, not allelic
Overall
CADD	24.4	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 0.0437% East Asian · 19/43,510 alleles

Filtering AF 0.0285% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0237%

Overall 0.00125% 20/1,595,542 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0437%	2,290
European (non-Finnish)	8.54e-05%	1,171,047

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: ARB2A
Protein: p.Ala283Val
Coding: c.848C>T
MANE Select: NM_032042
dbSNP: rs767399233
Type: single nucleotide variant
Location: chr5:93824206 (GRCh38)
Structure: AlphaFold pLDDT 84.01

Full ARB2A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ARB2A p.Ala271Val Uncertain significance ★ ⚠ same type
ARB2A p.Arg227Gly Uncertain significance ★ ⚠ same type
ARB2A p.Arg227Trp Uncertain significance ★ ⚠ same type
ARB2A p.Arg240Gln Uncertain significance ★ ⚠ same type
ARB2A p.Arg241Cys Uncertain significance ★ ⚠ same type
ARB2A p.Arg241His Uncertain significance ★ ⚠ same type
ARB2A p.Arg306Gln Uncertain significance ★ ⚠ same type
ARB2A p.Asn146Asp 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/arb2a-p-ala283val (accessed [today's date]).

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