Is APOA4 p.Asp335= (c.1005C>T) pathogenic?

APOA4 p.Asp335= (c.1005C>T) is classified Likely benign in APOA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-06). Ultra-rare (popmax 0.0111%, eas).

How common is APOA4 p.Asp335= (c.1005C>T) in the general population?

APOA4 p.Asp335= (c.1005C>T) is ultra-rare (popmax 0.0111%, eas) (gnomAD).

APOA4 p.Asp335=

c.1005C>T · rs545034382 · VCV763888

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0111%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.9	GERP -0.7
Overall
CADD	2.733	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0111% East Asian · 5/44,874 alleles

Filtering AF 0.00435% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00276%

Overall 0.0018% 29/1,614,164 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0111%	8,975
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
European (non-Finnish)	0.00169%	59,002
Admixed American	0.00167%	60,030
Remaining individualsnot grpmax-eligible	0.0016%	62,508
Finnishnot grpmax-eligible	0.00156%	64,012

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: APOA4
Protein: p.Asp335=
Coding: c.1005C>T
MANE Select: NM_000482
dbSNP: rs545034382
Type: single nucleotide variant
Location: chr11:116821053 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.14 · 2 PDB

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

Similar variants

APOA4 p.Asp335Asn Uncertain significance ★ ⚠ same residue
APOA4 p.Asp335His Uncertain significance ★ ⚠ same residue
APOA4 p.Asp335Val Uncertain significance ★ ⚠ same residue
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

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-asp335 (accessed [today's date]).

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