Is APOA1 p.Pro123= (c.369C>T) pathogenic?

APOA1 p.Pro123= (c.369C>T) is classified Likely benign in APOA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-21). Absent from gnomAD v4.1.

How common is APOA1 p.Pro123= (c.369C>T) in the general population?

APOA1 p.Pro123= (c.369C>T) is absent from gnomAD v4.1 (gnomAD).

APOA1 p.Pro123=

c.369C>T · VCV4914090

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Absent

absent from gnomAD v4.1

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 2.4	GERP 3.5, phastCons 1
Overall
CADD	12.77	PHRED · no single calibrated threshold — expert panels disagree

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: APOA1
Protein: p.Pro123=
Coding: c.369C>T
MANE Select: NM_000039
Type: single nucleotide variant
Location: chr11:116836243 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.66 · 31 PDB
Residue 123: the '10 x approximate tandem repeats' region; a UniProt-annotated variant site (in fha2; no protein expression); a UniProt-annotated variant site (in hdl deficiency; with periorbital xanthelasmas; decreased protein abundance); a UniProt-annotated variant site (in fha2; missing protein expression)

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

Similar variants

APOA1 p.Pro123Ser Uncertain significance ★★ ⚠ same residue
APOA1 p.Pro123Leu Uncertain significance ★ ⚠ same residue
APOA1 p.Pro123Thr 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
APOA1 p.Ala176Thr 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-pro123 (accessed [today's date]).

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