Is ABCD1 p.Leu504Phe (c.1510C>T) pathogenic?

ABCD1 p.Leu504Phe (c.1510C>T) is classified Likely pathogenic in ABCD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-27). AlphaMissense: likely pathogenic (0.9551); Absent from gnomAD v4.1.

How common is ABCD1 p.Leu504Phe (c.1510C>T) in the general population?

ABCD1 p.Leu504Phe (c.1510C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCD1 p.Leu504Phe (c.1510C>T)?

AlphaMissense predicts likely pathogenic (score 0.9551) — an in-silico prediction, not a clinical call.

ABCD1 p.Leu504Phe

c.1510C>T · rs2522296993 · VCV2574959

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9551 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9551	likely pathogenic ✓ concordant with ClinVar
REVEL	0.833	moderately pathogenic-leaning
SaProt	LLR -13.61	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	Δ0.30	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 4	GERP 0.73, phastCons 1
Regional constraint	o/e 0.69	unconstrained · MANE · 14 kb · p 4.8e-06 · regional, not allelic
Overall
CADD	26.5	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.Leu504Phe
Coding: c.1510C>T
MANE Select: NM_000033
dbSNP: rs2522296993
Type: single nucleotide variant
Location: chrX:153740113 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 504: a β-strand; the abc transporter domain

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

Similar variants

ABCD1 p.Leu504fs Likely pathogenic ★ 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
ABCD1 c.901-1G>A 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-leu504phe (accessed [today's date]).

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