Is ANGPT4 p.Lys148Arg (c.443A>G) pathogenic?

ANGPT4 p.Lys148Arg (c.443A>G) is classified Uncertain significance in ANGPT4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-26). AlphaMissense: likely benign (0.0991); Absent from gnomAD v4.1.

How common is ANGPT4 p.Lys148Arg (c.443A>G) in the general population?

ANGPT4 p.Lys148Arg (c.443A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ANGPT4 p.Lys148Arg (c.443A>G)?

AlphaMissense predicts likely benign (score 0.0991) — an in-silico prediction, not a clinical call.

ANGPT4 p.Lys148Arg

c.443A>G · VCV4049559

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0991 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0991	likely benign
REVEL	0.116	moderately benign-leaning
SaProt	LLR -5.88	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 1.1	GERP 1.8, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 43 kb · p 0.67 · regional, not allelic
Overall
CADD	20.0	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ANGPT4
Protein: p.Lys148Arg
Coding: c.443A>G
MANE Select: NM_015985
Type: single nucleotide variant
Location: chr20:890235 (GRCh38)
Gene constraint: LOEUF 1.189 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.33

Full ANGPT4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ANGPT4 p.Glu117= Benign ★★ same type
ANGPT4 p.Ser435= Benign ★★ same type
ANGPT4 p.Ala233Ser Uncertain significance ★ ⚠ same type
ANGPT4 p.Ala275Thr Uncertain significance ★ ⚠ same type
ANGPT4 p.Ala277Val Uncertain significance ★ ⚠ same type
ANGPT4 p.Ala279Asp Uncertain significance ★ ⚠ same type
ANGPT4 p.Ala445Thr Uncertain significance ★ ⚠ same type
ANGPT4 p.Arg242His 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/angpt4-p-lys148arg (accessed [today's date]).

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