Is APOA1 p.Arg140= (c.420C>T) pathogenic?

APOA1 p.Arg140= (c.420C>T) is classified Likely benign in APOA1 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-02). Very rare (popmax 0.00533%, afr).

How common is APOA1 p.Arg140= (c.420C>T) in the general population?

APOA1 p.Arg140= (c.420C>T) is very rare (popmax 0.00533%, afr) (gnomAD).

APOA1 p.Arg140=

c.420C>T · rs775173438 · VCV3022247

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00533%, 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 0.14	GERP 0.14, phastCons 0.003
Overall
CADD	15.54	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00533% African / African-American · 4/75,070 alleles

Filtering AF 0.00174% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.000616% 9/1,461,406 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.008%	12,501
African / African-Americangrpmax	0.00533%	18,768

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg140=
Coding: c.420C>T
MANE Select: NM_000039
dbSNP: rs775173438
Type: single nucleotide variant
Location: chr11:116836192 (GRCh38)
Gene constraint: LOEUF 1.168 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 73.66 · 31 PDB
Residue 140: 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.Arg140Leu Uncertain significance ★★ ⚠ same residue
APOA1 p.Arg140Cys Uncertain significance ★ ⚠ same residue
APOA1 p.Arg140Ser 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-arg140 (accessed [today's date]).

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