Is ABCD2 p.Gly477Arg (c.1429G>A) pathogenic?

ABCD2 p.Gly477Arg (c.1429G>A) is classified Uncertain significance in ABCD2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-04-03). AlphaMissense: likely pathogenic (0.7093); Ultra-rare (popmax 0.0117%, amr).

How common is ABCD2 p.Gly477Arg (c.1429G>A) in the general population?

ABCD2 p.Gly477Arg (c.1429G>A) is ultra-rare (popmax 0.0117%, amr) (gnomAD).

What do computational predictors say about ABCD2 p.Gly477Arg (c.1429G>A)?

AlphaMissense predicts likely pathogenic (score 0.7093) — an in-silico prediction, not a clinical call.

ABCD2 p.Gly477Arg

c.1429G>A · VCV3991736

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7093 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0117%, amr)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7093	likely pathogenic
REVEL	0.845	moderately pathogenic-leaning
SaProt	LLR -5.97	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.3, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 50 kb · p 0.028 · regional, not allelic
Overall
CADD	31.0	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 0.0117% Admixed American · 7/59,888 alleles

Filtering AF 0.00544% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00381%

Overall 0.00136% 22/1,612,050 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0117%	8,555
South Asian	0.0055%	18,192
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,556
African / African-American	0.00267%	37,463
Remaining individualsnot grpmax-eligible	0.0016%	62,404
European (non-Finnish)	0.000509%	196,457

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.Gly477Arg
Coding: c.1429G>A
MANE Select: NM_005164
Type: single nucleotide variant
Location: chr12:39603983 (GRCh38)
Gene constraint: LOEUF 0.714 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.65

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-gly477arg (accessed [today's date]).

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