Is ABRAXAS2 p.Ile381Phe (c.1141A>T) pathogenic?

ABRAXAS2 p.Ile381Phe (c.1141A>T) is classified Uncertain significance in ABRAXAS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). AlphaMissense: likely benign (0.0819); Very rare (popmax 0.00864%, nfe).

How common is ABRAXAS2 p.Ile381Phe (c.1141A>T) in the general population?

ABRAXAS2 p.Ile381Phe (c.1141A>T) is very rare (popmax 0.00864%, nfe) (gnomAD).

What do computational predictors say about ABRAXAS2 p.Ile381Phe (c.1141A>T)?

AlphaMissense predicts likely benign (score 0.0819) — an in-silico prediction, not a clinical call.

ABRAXAS2 p.Ile381Phe

c.1141A>T · VCV3994688

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0819 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00864%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0819	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -6.40	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 0.91	GERP 0.47, phastCons 0.98
Regional constraint	o/e 0.97	unconstrained · MANE · 3,612 bp · p 0.65 · regional, not allelic
Overall
CADD	16.93	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 0.00864% European (non-Finnish) · 102/1,180,032 alleles

Filtering AF 0.00724% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00676%

Overall 0.00651% 105/1,613,980 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00864%	11,569
Remaining individualsnot grpmax-eligible	0.0032%	31,241
Admixed American	0.00167%	59,978

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.Ile381Phe
Coding: c.1141A>T
MANE Select: NM_032182
Type: single nucleotide variant
Location: chr10:124834864 (GRCh38)
Gene constraint: LOEUF 0.641 · pLI 0.43 (gnomAD)
Structure: AlphaFold pLDDT 74.65 · 4 PDB
Residue 381: the 'disordered' region

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.Ala3Val Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Ala72Thr Uncertain significance ★ ⚠ same type
ABRAXAS2 p.Arg268Lys 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-ile381phe (accessed [today's date]).

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