Is ABCA2 p.Arg1101Cys (c.3301C>T) pathogenic?

ABCA2 p.Arg1101Cys (c.3301C>T) is classified Uncertain significance in ABCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-31). AlphaMissense: likely benign (0.0803); Very rare (popmax 0.00895%, nfe).

How common is ABCA2 p.Arg1101Cys (c.3301C>T) in the general population?

ABCA2 p.Arg1101Cys (c.3301C>T) is very rare (popmax 0.00895%, nfe) (gnomAD).

What do computational predictors say about ABCA2 p.Arg1101Cys (c.3301C>T)?

AlphaMissense predicts likely benign (score 0.0803) — an in-silico prediction, not a clinical call.

ABCA2 p.Arg1101Cys

c.3301C>T · rs771747170 · VCV3095344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0803 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00895%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.0803	likely benign
REVEL	0.495	indeterminate
SaProt	LLR -8.97	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP -2.7, phastCons 1
Regional constraint	o/e 0.59	unconstrained · MANE · 914 bp · p 3.8e-13 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R1100C vs ClinVar R1101C) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00895% European (non-Finnish) · 104/1,161,446 alleles

Filtering AF 0.00753% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00703%

Overall 0.00747% 118/1,578,952 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00895%	11,168
Finnishnot grpmax-eligible	0.00668%	14,969
South Asian	0.00443%	22,592
Remaining individualsnot grpmax-eligible	0.00326%	30,677
African / African-American	0.00287%	34,810
East Asian	0.00229%	43,712
Admixed American	0.00177%	56,370

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.Arg1101Cys
Coding: c.3301C>T
MANE Select: NM_001606
dbSNP: rs771747170
Type: single nucleotide variant
Location: chr9:137015978 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 1101: the abc transporter 1 domain; 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.Arg1101His Uncertain significance ★ ⚠ same residue
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

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-arg1101cys (accessed [today's date]).

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