Is ABRA p.Val189Ile (c.565G>A) pathogenic?

ABRA p.Val189Ile (c.565G>A) is classified Likely benign in ABRA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-07). AlphaMissense: likely benign (0.0649); Ultra-rare (popmax 0.0133%, amr).

How common is ABRA p.Val189Ile (c.565G>A) in the general population?

ABRA p.Val189Ile (c.565G>A) is ultra-rare (popmax 0.0133%, amr) (gnomAD).

What do computational predictors say about ABRA p.Val189Ile (c.565G>A)?

AlphaMissense predicts likely benign (score 0.0649) — an in-silico prediction, not a clinical call.

ABRA p.Val189Ile

c.565G>A · VCV3329257

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0649 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0649	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -7.30	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 -7.9	GERP -5.3
Regional constraint	o/e 1.02	unconstrained · MANE · 9,150 bp · p 0.68 · regional, not allelic
Overall
CADD	0.017	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 0.0133% Admixed American · 8/60,002 alleles

Filtering AF 0.00661% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00482%

Overall 0.00378% 61/1,614,086 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0133%	7,500
European (non-Finnish)	0.00407%	24,584
African / African-American	0.004%	24,978
East Asian	0.00223%	44,886
Finnishnot grpmax-eligible	0.00156%	64,036

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.Val189Ile
Coding: c.565G>A
MANE Select: NM_139166
Type: single nucleotide variant
Location: chr8:106769626 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.14
Residue 189: 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.Arg120Thr 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

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-val189ile (accessed [today's date]).

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