Is ABTB3 p.Arg519Ser (c.1555C>A) pathogenic?

ABTB3 p.Arg519Ser (c.1555C>A) is classified Uncertain significance in ABTB3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-14). AlphaMissense: likely pathogenic (0.995); No allele count reported in gnomAD v4.1 (AN 1,535,302).

How common is ABTB3 p.Arg519Ser (c.1555C>A) in the general population?

ABTB3 p.Arg519Ser (c.1555C>A) is no allele count reported in gnomAD v4.1 (AN 1,535,302) (gnomAD).

What do computational predictors say about ABTB3 p.Arg519Ser (c.1555C>A)?

AlphaMissense predicts likely pathogenic (score 0.995) — an in-silico prediction, not a clinical call.

ABTB3 p.Arg519Ser

c.1555C>A · VCV3454013

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.995 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,535,302)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.995	likely pathogenic · top 7% in ABTB3
REVEL	0.437	indeterminate
SaProt	LLR -13.89	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.6	GERP 1.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 291 kb · p 0.39 · regional, not allelic
Overall
CADD	25.5	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

No allele count reported in gnomAD v4.1 (AN 1,535,302). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABTB3
Protein: p.Arg519Ser
Coding: c.1555C>A
MANE Select: NM_001018072
Type: single nucleotide variant
Location: chr12:107581216 (GRCh38)
Structure: AlphaFold pLDDT 73.18

Full ABTB3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABTB3 c.1135+525T>A Uncertain significance ★ same type
ABTB3 p.Ala1019Val Uncertain significance ★ same type
ABTB3 p.Ala119Glu Uncertain significance ★ ⚠ same type
ABTB3 p.Ala130Thr Uncertain significance ★ ⚠ same type
ABTB3 p.Ala147Ser Uncertain significance ★ ⚠ same type
ABTB3 p.Ala147Val Uncertain significance ★ ⚠ same type
ABTB3 p.Ala176Glu Uncertain significance ★ ⚠ same type
ABTB3 p.Ala176Ser 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/abtb3-p-arg519ser (accessed [today's date]).

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