Is APOA4 p.Thr85= (c.255C>T) pathogenic?

APOA4 p.Thr85= (c.255C>T) is classified Likely benign in APOA4 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-05-15). Ultra-rare (popmax 0.0308%, afr).

How common is APOA4 p.Thr85= (c.255C>T) in the general population?

APOA4 p.Thr85= (c.255C>T) is ultra-rare (popmax 0.0308%, afr) (gnomAD).

APOA4 p.Thr85=

c.255C>T · rs763552085 · VCV2051299

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0308%, afr)

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 -11	GERP -7.1
Overall
CADD	0.17	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0308% African / African-American · 23/74,568 alleles

Filtering AF 0.0211% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0179%

Overall 0.00381% 61/1,600,916 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0308%	3,242
East Asian	0.00892%	11,205
Remaining individualsnot grpmax-eligible	0.00805%	12,419
European (non-Finnish)	0.0024%	41,718
Admixed American	0.00167%	59,990

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.Thr85=
Coding: c.255C>T
MANE Select: NM_000482
dbSNP: rs763552085
Type: single nucleotide variant
Location: chr11:116821803 (GRCh38)
Gene constraint: LOEUF 0.985 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.14 · 2 PDB
Residue 85: the '13 x 22 aa approximate tandem repeats' region

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

Similar variants

APOA4 p.Thr85Ile 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
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-thr85 (accessed [today's date]).

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