Is ABCA2 p.Ala133Val (c.398C>T) pathogenic?

ABCA2 p.Ala133Val (c.398C>T) is classified Likely benign in ABCA2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-05). AlphaMissense: likely benign (0.1019); Low-frequency (popmax 4.92%, sas); Associated with ABCA2-related disorder.

What condition is associated with ABCA2 p.Ala133Val (c.398C>T)?

ABCA2 p.Ala133Val (c.398C>T) is associated with ABCA2-related disorder (ClinVar).

How common is ABCA2 p.Ala133Val (c.398C>T) in the general population?

ABCA2 p.Ala133Val (c.398C>T) is low-frequency (popmax 4.92%, sas) (gnomAD).

What do computational predictors say about ABCA2 p.Ala133Val (c.398C>T)?

AlphaMissense predicts likely benign (score 0.1019) — an in-silico prediction, not a clinical call.

ABCA2 p.Ala133Val

c.398C>T · rs551444612 · VCV3042255

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1019 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 4.92%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCA2-related disorder

Computational evidence

Protein change
AlphaMissense	0.1019	likely benign
REVEL	0.153	moderately benign-leaning
SaProt	LLR -7.33	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -0.052, phastCons 0.002
Regional constraint	o/e 1.07	unconstrained · MANE · 2,023 bp · p 0.16 · regional, not allelic
Overall
CADD	14.27	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM A132V vs ClinVar A133V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.92% South Asian · 4,400/89,508 alleles

Filtering AF 4.79% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.74%

Overall 0.287% 4,612/1,604,856 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	4.92%	20
Remaining individualsnot grpmax-eligible	0.264%	379
Middle Eastern	0.108%	922
East Asian	0.00672%	14,875
African / African-American	0.00534%	18,734
Admixed American	0.00336%	29,719
European (non-Finnish)	0.0028%	35,686

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.Ala133Val
Coding: c.398C>T
MANE Select: NM_001606
dbSNP: rs551444612
Type: single nucleotide variant
Location: chr9:137022743 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46

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

Disease context

ABCA2-related disorder

Similar variants

ABCA2 p.Gln1370Ter Likely pathogenic ★★ same condition
ABCA2 p.Ala1357Thr Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg2392Gln Uncertain significance ★★ ⚠ same condition
ABCA2 p.Glu1515Lys Uncertain significance ★★ ⚠ same condition
ABCA2 p.Ser1427Arg Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg2298Trp Uncertain significance ★ ⚠ same condition
ABCA2 p.Arg926Trp Uncertain significance ★ ⚠ same condition
ABCA2 p.Thr398Lys Conflicting classifications of pathogenicity ★ ⚠ same condition

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-ala133val (accessed [today's date]).

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