Is ABCD2 p.Arg582Cys (c.1744C>T) pathogenic?

ABCD2 p.Arg582Cys (c.1744C>T) is classified Likely benign in ABCD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-11). AlphaMissense: likely benign (0.069); Rare (popmax 0.115%, sas).

How common is ABCD2 p.Arg582Cys (c.1744C>T) in the general population?

ABCD2 p.Arg582Cys (c.1744C>T) is rare (popmax 0.115%, sas) (gnomAD).

What do computational predictors say about ABCD2 p.Arg582Cys (c.1744C>T)?

AlphaMissense predicts likely benign (score 0.069) — an in-silico prediction, not a clinical call.

ABCD2 p.Arg582Cys

c.1744C>T · rs200462514 · VCV2301033

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.069 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.115%, sas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.069	likely benign
REVEL	0.294	indeterminate
SaProt	LLR -8.52	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.36 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.23	GERP -5.3
Regional constraint	o/e 0.88	unconstrained · MANE · 50 kb · p 0.028 · regional, not allelic
Overall
CADD	12.47	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% South Asian · 105/90,982 alleles

Filtering AF 0.0975% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0908%

Overall 0.0101% 163/1,613,398 alleles · rare exomes 142/1,461,124 · genomes 21/152,274 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.115%	866
Admixed American	0.0434%	2,306
East Asian	0.0156%	6,406
Remaining individualsnot grpmax-eligible	0.0128%	7,811
African / African-American	0.00667%	15,004
European (non-Finnish)	0.00102%	98,296

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: ABCD2
Protein: p.Arg582Cys
Coding: c.1744C>T
MANE Select: NM_005164
dbSNP: rs200462514
Type: single nucleotide variant
Location: chr12:39586200 (GRCh38)
Gene constraint: LOEUF 0.714 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.65
Residue 582: the abc transporter domain

Full ABCD2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCD2 c.1878-18G>C Benign/Likely benign ★★ same type
ABCD2 p.Ala251Gly Uncertain significance ★ ⚠ same type
ABCD2 p.Ala273Thr Uncertain significance ★ ⚠ same type
ABCD2 p.Ala489Glu Uncertain significance ★ same type
ABCD2 p.Arg16Thr Uncertain significance ★ ⚠ same type
ABCD2 p.Arg178Cys Uncertain significance ★ ⚠ same type
ABCD2 p.Arg178His Uncertain significance ★ ⚠ same type
ABCD2 p.Arg337Cys 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/abcd2-p-arg582cys (accessed [today's date]).

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