Is ABCD1 p.Leu253Val (c.757C>G) pathogenic?

ABCD1 p.Leu253Val (c.757C>G) is classified Benign/Likely benign in ABCD1 (ClinVar, Multiple submitters, 15 submitters; last evaluated 2026-03-01). AlphaMissense: likely benign (0.076); Rare (popmax 0.147%, nfe); Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Leu253Val (c.757C>G)?

ABCD1 p.Leu253Val (c.757C>G) is associated with Inborn genetic diseases, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Leu253Val (c.757C>G) in the general population?

ABCD1 p.Leu253Val (c.757C>G) is rare (popmax 0.147%, nfe) (gnomAD).

What do computational predictors say about ABCD1 p.Leu253Val (c.757C>G)?

AlphaMissense predicts likely benign (score 0.076) — an in-silico prediction, not a clinical call.

ABCD1 p.Leu253Val

c.757C>G · rs150151955 · VCV377034

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 15 submitters

AlphaMissense

likely benign

0.076 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.147%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.076	likely benign
REVEL	0.608	indeterminate
SaProt	LLR -6.07	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP -3.7, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 865 bp · p 0.3 · regional, not allelic
Overall
CADD	17.29	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 0.147% European (non-Finnish) · 1,308/891,540 alleles

Filtering AF 0.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.137%

Overall 0.119% 1,439/1,204,688 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.147%	682
Remaining individualsnot grpmax-eligible	0.123%	816
Finnishnot grpmax-eligible	0.11%	913
African / African-American	0.026%	3,852
South Asian	0.0071%	14,093
Admixed American	0.00656%	15,236
Ashkenazi Jewishnot grpmax-eligible	0.00461%	21,690

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: ABCD1
Protein: p.Leu253Val
Coding: c.757C>G
MANE Select: NM_000033
dbSNP: rs150151955
Type: single nucleotide variant
Location: chrX:153726023 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 253: an α-helix; the abc transmembrane type-1 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: adrenoleukodystrophy

Similar variants

ABCD1 p.Leu253Phe Uncertain significance ★★ ⚠ same residue
ABCD1 c.1635-2A>G Pathogenic ★★ same condition
ABCD1 c.1781-1G>C Pathogenic ★★ same condition
ABCD1 c.1781-1G>T Pathogenic/Likely pathogenic ★★ same condition
ABCD1 c.1866-10G>A Pathogenic/Likely pathogenic ★★ same condition
ABCD1 c.1866-1G>C Likely pathogenic ★★ same condition
ABCD1 c.1866-2A>T Likely pathogenic ★★ same condition
ABCD1 c.901-1G>A Pathogenic ★★ same condition

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-leu253val (accessed [today's date]).

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