Is ABCD3 p.Arg157Lys (c.470G>A) pathogenic?

ABCD3 p.Arg157Lys (c.470G>A) is classified Uncertain significance in ABCD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-20). AlphaMissense: ambiguous (0.3436); Ultra-rare (popmax 0.0179%, mid).

How common is ABCD3 p.Arg157Lys (c.470G>A) in the general population?

ABCD3 p.Arg157Lys (c.470G>A) is ultra-rare (popmax 0.0179%, mid) (gnomAD).

What do computational predictors say about ABCD3 p.Arg157Lys (c.470G>A)?

AlphaMissense predicts ambiguous (score 0.3436) — an in-silico prediction, not a clinical call.

ABCD3 p.Arg157Lys

c.470G>A · rs201088281 · VCV2422114

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3436 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, mid)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3436	ambiguous
REVEL	0.795	moderately pathogenic-leaning
SaProt	LLR -8.56	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 10	phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 23 kb · p 3.7e-09 · regional, not allelic
Overall
CADD	24.8	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 0.0179% Middle Eastern · 1/5,586 alleles

Filtering AF 0.00379% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00346%

Overall 0.00387% 62/1,603,492 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0179%	5,586
European (non-Finnish)	0.00486%	20,597
East Asian	0.00224%	44,646
Remaining individualsnot grpmax-eligible	0.00161%	61,952
African / African-American	0.00134%	74,726
South Asian	0.00112%	89,510

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: ABCD3
Protein: p.Arg157Lys
Coding: c.470G>A
MANE Select: NM_002858
dbSNP: rs201088281
Type: single nucleotide variant
Location: chr1:94475207 (GRCh38)
Gene constraint: LOEUF 0.484 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 83.39 · 9 PDB
Residue 157: an α-helix; the abc transmembrane type-1 domain

Full ABCD3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

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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/abcd3-p-arg157lys (accessed [today's date]).

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