Is APOA4 p.Asp33Asn (c.97G>A) pathogenic?

APOA4 p.Asp33Asn (c.97G>A) is classified Pathogenic in APOA4 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2025-02-26). AlphaMissense: likely benign (0.1099); Absent from gnomAD v4.1; Associated with tubulointerstitial kidney disease, autosomal dominant 6.

What condition is associated with APOA4 p.Asp33Asn (c.97G>A)?

APOA4 p.Asp33Asn (c.97G>A) is associated with tubulointerstitial kidney disease, autosomal dominant 6 (ClinVar).

How common is APOA4 p.Asp33Asn (c.97G>A) in the general population?

APOA4 p.Asp33Asn (c.97G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about APOA4 p.Asp33Asn (c.97G>A)?

AlphaMissense predicts likely benign (score 0.1099) — an in-silico prediction, not a clinical call.

APOA4 p.Asp33Asn

c.97G>A · VCV3764741

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1099 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

tubulointerstitial kidney disease, autosomal dominant 6

Computational evidence

Protein change
AlphaMissense	0.1099	likely benign ⚠ discordant with ClinVar
REVEL	0.314	indeterminate
SaProt	LLR -6.69	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.32	GERP 1.9, phastCons 0.99
Regional constraint	o/e 1.08	unconstrained · MANE · 2,321 bp · p 0.088 · regional, not allelic
Overall
CADD	15.36	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

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: APOA4
Protein: p.Asp33Asn
Coding: c.97G>A
MANE Select: NM_000482
Type: single nucleotide variant
Location: chr11:116822738 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.14 · 2 PDB
Residue 33: the '13 x 22 aa approximate tandem repeats' region; a UniProt-annotated variant site (in adtkd6; likely pathogenic)

Full APOA4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

tubulointerstitial kidney disease, autosomal dominant 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

APOA4 p.Leu66Val Pathogenic ⚠ same condition
APOA4 p.Ala172Thr Uncertain significance ★★ ⚠ same type
APOA4 p.Ala333Val Uncertain significance ★★ ⚠ same type
APOA4 p.Ala60Asp Uncertain significance ★★ ⚠ same type
APOA4 p.Arg166Ser Uncertain significance ★★ ⚠ same type
APOA4 p.Arg275Cys Uncertain significance ★★ ⚠ same type
APOA4 p.Gln50Arg Uncertain significance ★★ ⚠ same type
APOA4 p.Gln50Lys 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/apoa4-p-asp33asn (accessed [today's date]).

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