Is APOA1 p.Arg34Ter (c.100C>T) pathogenic?

APOA1 p.Arg34Ter (c.100C>T) is classified Pathogenic in APOA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-23). Very rare (popmax 0.00102%, nfe).

How common is APOA1 p.Arg34Ter (c.100C>T) in the general population?

APOA1 p.Arg34Ter (c.100C>T) is very rare (popmax 0.00102%, nfe) (gnomAD).

APOA1 p.Arg34Ter

c.100C>T · rs1373700967 · VCV2137256

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00102%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 4
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.1	GERP 0.1, phastCons 0.62
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00102% European (non-Finnish) · 12/1,179,956 alleles

Filtering AF 0.000542% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000428%

Overall 0.000821% 12/1,461,682 alleles · very rare

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: APOA1
Protein: p.Arg34Ter
Coding: c.100C>T
MANE Select: NM_000039
dbSNP: rs1373700967
Type: single nucleotide variant
Location: chr11:116837101 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.66 · 31 PDB
Residue 34: a UniProt-annotated variant site (in fha2; no protein expression); a UniProt-annotated variant site (in baltimore); an α-helix

Full APOA1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

APOA1 p.Arg34Gly Uncertain significance ★★ ⚠ same residue
APOA1 p.Arg34Leu Uncertain significance ★★ ⚠ same residue
APOA1 p.Arg34= Likely benign ★★ same residue
APOA1 p.Arg34Gln Uncertain significance ★ ⚠ same residue
APOA1 p.Arg197Pro Pathogenic ★★ same type
APOA1 p.Gln23Ter Pathogenic ★★ same type
APOA1 p.Gly50Arg Pathogenic ★★ same type
APOA1 c.-21+22G>A 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/apoa1-p-arg34ter (accessed [today's date]).

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