Is ABCD3 p.Ala580Val (c.1739C>T) pathogenic?

ABCD3 p.Ala580Val (c.1739C>T) is classified Uncertain significance in ABCD3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-19). AlphaMissense: likely pathogenic (0.9812); Ultra-rare (popmax 0.0187%, afr).

How common is ABCD3 p.Ala580Val (c.1739C>T) in the general population?

ABCD3 p.Ala580Val (c.1739C>T) is ultra-rare (popmax 0.0187%, afr) (gnomAD).

What do computational predictors say about ABCD3 p.Ala580Val (c.1739C>T)?

AlphaMissense predicts likely pathogenic (score 0.9812) — an in-silico prediction, not a clinical call.

ABCD3 p.Ala580Val

c.1739C>T · VCV4796902

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9812 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, afr)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9812	likely pathogenic
REVEL	0.918	moderately pathogenic-leaning
SaProt	LLR -13.15	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 0.95, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 29 kb · p 0.00033 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

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

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0187% African / African-American · 14/74,990 alleles

Filtering AF 0.0112% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00904%

Overall 0.00267% 43/1,613,220 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0187%	5,356
South Asian	0.00879%	11,383
Remaining individualsnot grpmax-eligible	0.0048%	20,815
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,568
Admixed American	0.00334%	29,974
European (non-Finnish)	0.00127%	78,633

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.Ala580Val
Coding: c.1739C>T
MANE Select: NM_002858
Type: single nucleotide variant
Location: chr1:94499613 (GRCh38)
Gene constraint: LOEUF 0.484 · pLI 0.99 (gnomAD)
Structure: AlphaFold pLDDT 83.39 · 9 PDB
Residue 580: the abc transporter domain; an α-helix

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

Similar variants

ABCD3 p.Ala580= Likely benign ★ same residue
ABCD3 p.Ala131Thr Uncertain significance ★★ ⚠ same type
ABCD3 p.Ala3Val Uncertain significance ★★ ⚠ same type
ABCD3 p.Arg496Cys Uncertain significance ★★ ⚠ same type
ABCD3 p.Asn12Tyr Uncertain significance ★★ ⚠ same type
ABCD3 p.Ile225Val Uncertain significance ★★ ⚠ same type
ABCD3 p.Leu23Val Uncertain significance ★★ ⚠ same type
ABCD3 p.Leu45Val 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/abcd3-p-ala580val (accessed [today's date]).

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