Is ABCD1 p.Ile643Phe (c.1927A>T) pathogenic?

ABCD1 p.Ile643Phe (c.1927A>T) is classified Uncertain significance in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-16). AlphaMissense: likely pathogenic (0.7437); Absent from gnomAD v4.1.

How common is ABCD1 p.Ile643Phe (c.1927A>T) in the general population?

ABCD1 p.Ile643Phe (c.1927A>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD1 p.Ile643Phe (c.1927A>T)?

AlphaMissense predicts likely pathogenic (score 0.7437) — an in-silico prediction, not a clinical call.

ABCD1 p.Ile643Phe

c.1927A>T · rs2091773850 · VCV2438765

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7437 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7437	likely pathogenic
REVEL	0.897	moderately pathogenic-leaning
SaProt	LLR -12.51	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 11	GERP 1.6, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 3,261 bp · p 4e-11 · regional, not allelic
Overall
CADD	28.3	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

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.Ile643Phe
Coding: c.1927A>T
dbSNP: rs2091773850
Type: single nucleotide variant
Location: chrX:153743282 (GRCh38)

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

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-ile643phe (accessed [today's date]).

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