Is ABAT p.Arg281Leu (c.842G>T) pathogenic?

ABAT p.Arg281Leu (c.842G>T) is classified Uncertain significance in ABAT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-11). AlphaMissense: likely benign (0.2986); Very rare (popmax 0.0011%, sas); Associated with Inborn genetic diseases.

What condition is associated with ABAT p.Arg281Leu (c.842G>T)?

ABAT p.Arg281Leu (c.842G>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABAT p.Arg281Leu (c.842G>T) in the general population?

ABAT p.Arg281Leu (c.842G>T) is very rare (popmax 0.0011%, sas) (gnomAD).

What do computational predictors say about ABAT p.Arg281Leu (c.842G>T)?

AlphaMissense predicts likely benign (score 0.2986) — an in-silico prediction, not a clinical call.

ABAT p.Arg281Leu

c.842G>T · VCV3932645

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2986 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2986	likely benign
REVEL	0.692	pathogenic-leaning
SaProt	LLR -7.17	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 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 46 kb · p 0.32 · regional, not allelic
Overall
CADD	26.2	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 0.0011% South Asian · 1/91,070 alleles

Overall 6.84e-05% 1/1,461,858 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: ABAT
Protein: p.Arg281Leu
Coding: c.842G>T
MANE Select: NM_020686
Type: single nucleotide variant
Location: chr16:8772805 (GRCh38)
Gene constraint: LOEUF 0.871 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 93.91

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABAT p.Arg281Gln Uncertain significance ★ ⚠ same residue
ABAT p.Arg281Trp Uncertain significance ★ ⚠ same residue
ABAT p.Leu211Phe Pathogenic/Likely pathogenic ★★ same condition
ABAT p.Ala411Asp Uncertain significance ★★ ⚠ same condition
ABAT p.Ala70Ser Uncertain significance ★★ ⚠ same condition
ABAT p.Arg19Ser Uncertain significance ★★ ⚠ same condition
ABAT p.Arg313Thr Uncertain significance ★★ ⚠ same condition
ABAT p.Arg317Lys Uncertain significance ★★ ⚠ same condition

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/abat-p-arg281leu (accessed [today's date]).

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