Is ABRAXAS2 p.Ala3Val (c.8C>T) pathogenic?

ABRAXAS2 p.Ala3Val (c.8C>T) is classified Uncertain significance in ABRAXAS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely pathogenic (0.8736); Very rare (popmax 0.000254%, nfe).

How common is ABRAXAS2 p.Ala3Val (c.8C>T) in the general population?

ABRAXAS2 p.Ala3Val (c.8C>T) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about ABRAXAS2 p.Ala3Val (c.8C>T)?

AlphaMissense predicts likely pathogenic (score 0.8736) — an in-silico prediction, not a clinical call.

ABRAXAS2 p.Ala3Val

c.8C>T · VCV4188434

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8736 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8736	likely pathogenic
REVEL	0.18	moderately benign-leaning
SaProt	LLR -8.90	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.9, phastCons 1
Regional constraint	o/e 1.70	unconstrained · MANE · 62 bp · p 0.00022 · regional, not allelic
Overall
CADD	27.3	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000254% European (non-Finnish) · 3/1,179,764 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000205% 3/1,461,164 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: ABRAXAS2
Protein: p.Ala3Val
Coding: c.8C>T
MANE Select: NM_032182
Type: single nucleotide variant
Location: chr10:124801837 (GRCh38)
Gene constraint: LOEUF 0.641 · pLI 0.43 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 4 PDB
Residue 3: the mpn domain; a β-strand

Full ABRAXAS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABRAXAS2 p.Ala161Asp Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Ala161Ser Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Ala208Thr Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Ala208Val Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Ala301Ser Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Ala72Thr Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Arg268Lys Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Arg282Trp 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/abraxas2-p-ala3val (accessed [today's date]).

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