Is ABRA p.Ser188Arg (c.564C>G) pathogenic?

ABRA p.Ser188Arg (c.564C>G) is classified Uncertain significance in ABRA (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely pathogenic (0.8546); Ultra-rare (popmax 0.0156%, eas).

How common is ABRA p.Ser188Arg (c.564C>G) in the general population?

ABRA p.Ser188Arg (c.564C>G) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

What do computational predictors say about ABRA p.Ser188Arg (c.564C>G)?

AlphaMissense predicts likely pathogenic (score 0.8546) — an in-silico prediction, not a clinical call.

ABRA p.Ser188Arg

c.564C>G · rs770028905 · VCV3132527

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8546 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.8546	likely pathogenic
REVEL	0.367	indeterminate
SaProt	LLR -7.82	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -3, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 9,150 bp · p 0.68 · regional, not allelic
Overall
CADD	17.62	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 0.0156% East Asian · 7/44,886 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00514%

Overall 0.000434% 7/1,614,002 alleles · ultra-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.Ser188Arg
Coding: c.564C>G
MANE Select: NM_139166
dbSNP: rs770028905
Type: single nucleotide variant
Location: chr8:106769627 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.14
Residue 188: a modified residue (phosphoserine); 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-ser188arg (accessed [today's date]).

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