Is ABCD1 p.Ser340= (c.1020C>T) pathogenic?

ABCD1 p.Ser340= (c.1020C>T) is classified Likely benign in ABCD1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-04-23). Very rare (popmax 0.00434%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABCD1 p.Ser340= (c.1020C>T)?

ABCD1 p.Ser340= (c.1020C>T) is associated with Inborn genetic diseases, adrenoleukodystrophy (ClinVar).

How common is ABCD1 p.Ser340= (c.1020C>T) in the general population?

ABCD1 p.Ser340= (c.1020C>T) is very rare (popmax 0.00434%, amr) (gnomAD).

ABCD1 p.Ser340=

c.1020C>T · rs781828983 · VCV1157843

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.00434%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>G here scores Δ0.32 · evaluated, not missing
Constraint at this position
Conservation	phyloP -8.2	GERP -3.5
Overall
CADD	1.367	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00434% Admixed American · 2/46,086 alleles

Filtering AF 0.000719% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000269%

Overall 0.000546% 6/1,097,948 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00434%	23,043
South Asian	0.00175%	56,998
European (non-Finnish)	0.000335%	298,434

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.Ser340=
Coding: c.1020C>T
MANE Select: NM_000033
dbSNP: rs781828983
Type: single nucleotide variant
Location: chrX:153729351 (GRCh38)
Structure: AlphaFold pLDDT 81.58 · 14 PDB
Residue 340: 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.Ser340Arg Uncertain significance ★★ ⚠ same residue
ABCD1 p.Ser340Asn Conflicting classifications of pathogenicity ★ ⚠ 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

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-ser340 (accessed [today's date]).

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