Is ABCA2 p.Thr440= (c.1320G>A) pathogenic?

ABCA2 p.Thr440= (c.1320G>A) is classified Likely benign in ABCA2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2026-06-01). Rare (popmax 0.862%, amr).

How common is ABCA2 p.Thr440= (c.1320G>A) in the general population?

ABCA2 p.Thr440= (c.1320G>A) is rare (popmax 0.862%, amr) (gnomAD).

ABCA2 p.Thr440=

c.1320G>A · rs56164699 · VCV1299165

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

rare (popmax 0.862%, amr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.296	indeterminate
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.31 · evaluated, not missing
Constraint at this position
Conservation	phyloP -10	GERP -2.2
Overall
CADD	4.073	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.862% Admixed American · 517/59,958 alleles

Filtering AF 0.801% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.776%

Overall 0.543% 8,754/1,611,724 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.95%	51
Admixed Americangrpmax	0.862%	116
Remaining individualsnot grpmax-eligible	0.633%	158
European (non-Finnish)	0.577%	173
Finnishnot grpmax-eligible	0.237%	422
Middle Eastern	0.233%	429
South Asian	0.193%	517
African / African-American	0.16%	625
East Asian	0.00669%	14,954

Ashkenazi Jewish 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: ABCA2
Protein: p.Thr440=
Coding: c.1320G>A
MANE Select: NM_001606
dbSNP: rs56164699
Type: single nucleotide variant
Location: chr9:137020441 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 440: a UniProt-annotated variant site (in idpogsa)

Full ABCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA2 p.Gln1370Ter Likely pathogenic ★★ same type
ABCA2 c.3883-3C>T Uncertain significance ★★ same type
ABCA2 p.Ala1357Thr Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1620Thr Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1645Val Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1715Ser Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala2180Thr Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala2206Val 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/abca2-p-thr440 (accessed [today's date]).

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