Is ABCD1 p.Thr693Pro (c.2077A>C) pathogenic?

ABCD1 p.Thr693Pro (c.2077A>C) is classified Uncertain significance in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-23). AlphaMissense: likely benign (0.3254); Absent from gnomAD v4.1.

How common is ABCD1 p.Thr693Pro (c.2077A>C) in the general population?

ABCD1 p.Thr693Pro (c.2077A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD1 p.Thr693Pro (c.2077A>C)?

AlphaMissense predicts likely benign (score 0.3254) — an in-silico prediction, not a clinical call.

ABCD1 p.Thr693Pro

c.2077A>C · VCV4530964

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3254 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3254	likely benign
REVEL	0.311	indeterminate
SaProt	LLR -12.04	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 1.7, phastCons 1
Regional constraint	o/e 0.70	unconstrained · MANE · 242 bp · p 0.011 · regional, not allelic
Overall
CADD	21.3	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCD1
Protein: p.Thr693Pro
Coding: c.2077A>C
MANE Select: NM_000033
Type: single nucleotide variant
Location: chrX:153743574 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 693: the 'required for homodimerization' region; a UniProt-annotated variant site (in ald); an α-helix; the abc transporter domain

Full ABCD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCD1 p.Thr693Met Uncertain significance ★★ ⚠ same residue
ABCD1 p.Thr693= Likely benign ★★ same residue
ABCD1 c.1635-2A>G Pathogenic ★★ same type
ABCD1 c.1781-1G>C Pathogenic ★★ same type
ABCD1 c.1781-1G>T Pathogenic/Likely pathogenic ★★ same type
ABCD1 c.1866-10G>A Pathogenic/Likely pathogenic ★★ same type
ABCD1 c.1866-1G>C Likely pathogenic ★★ same type
ABCD1 c.1866-2A>T Likely pathogenic ★★ 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/abcd1-p-thr693pro (accessed [today's date]).

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