Is ABAT p.Ile449Leu (c.1345A>T) pathogenic?

ABAT p.Ile449Leu (c.1345A>T) is classified Uncertain significance in ABAT (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-20). AlphaMissense: likely benign (0.0765); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with ABAT p.Ile449Leu (c.1345A>T)?

ABAT p.Ile449Leu (c.1345A>T) is associated with Inborn genetic diseases (ClinVar).

How common is ABAT p.Ile449Leu (c.1345A>T) in the general population?

ABAT p.Ile449Leu (c.1345A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABAT p.Ile449Leu (c.1345A>T)?

AlphaMissense predicts likely benign (score 0.0765) — an in-silico prediction, not a clinical call.

ABAT p.Ile449Leu

c.1345A>T · VCV3932723

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0765 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,614,186)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0765	likely benign
REVEL	0.151	moderately benign-leaning
SaProt	LLR -6.69	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 -0.17	GERP -3.3
Regional constraint	o/e 0.96	unconstrained · MANE · 46 kb · p 0.32 · regional, not allelic
Overall
CADD	0.164	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

No allele count reported in gnomAD v4.1 (AN 1,614,186). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ABAT
Protein: p.Ile449Leu
Coding: c.1345A>T
MANE Select: NM_020686
Type: single nucleotide variant
Location: chr16:8779554 (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.Ile449Thr Uncertain significance ★ ⚠ same residue
ABAT p.Ile449Val 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-ile449leu (accessed [today's date]).

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