Is ABRA p.Arg120Thr (c.359G>C) pathogenic?

ABRA p.Arg120Thr (c.359G>C) is classified Uncertain significance in ABRA (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: likely benign (0.2065); Very rare (popmax 8.47e-05%, nfe).

How common is ABRA p.Arg120Thr (c.359G>C) in the general population?

ABRA p.Arg120Thr (c.359G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about ABRA p.Arg120Thr (c.359G>C)?

AlphaMissense predicts likely benign (score 0.2065) — an in-silico prediction, not a clinical call.

ABRA p.Arg120Thr

c.359G>C · VCV3796131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2065 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2065	likely benign
REVEL	0.72	pathogenic-leaning
SaProt	LLR -6.18	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4	GERP 0.92, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 9,150 bp · p 0.68 · regional, not allelic
Overall
CADD	23.9	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 8.47e-05% European (non-Finnish) · 1/1,180,034 alleles

Overall 6.84e-05% 1/1,461,892 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: ABRA
Protein: p.Arg120Thr
Coding: c.359G>C
MANE Select: NM_139166
Type: single nucleotide variant
Location: chr8:106769832 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.14
Residue 120: the 'disordered' region

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

Similar variants

ABRA p.Ala37Val Uncertain significance ★ ⚠ same type
ABRA p.Ala62Thr Uncertain significance ★ ⚠ same type
ABRA p.Ala62Val Uncertain significance ★ ⚠ same type
ABRA p.Arg149Ser Uncertain significance ★ ⚠ same type
ABRA p.Arg159Trp Uncertain significance ★ ⚠ same type
ABRA p.Arg203Lys Uncertain significance ★ ⚠ same type
ABRA p.Arg218Cys Uncertain significance ★ ⚠ same type
ABRA p.Arg218His 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/abra-p-arg120thr (accessed [today's date]).

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