Is ABCD4 c.1636+258del pathogenic?

ABCD4 c.1636+258del is classified Benign in ABCD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-08-18). Common (popmax 38.6%, nfe) — too common for a highly-penetrant pathogenic allele.

ABCD4 c.1636+258del

Q: How common is ABCD4 c.1636+258del in the general population?

ABCD4 c.1636+258del is common (popmax 38.6%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

rs67310859 · VCV1181427

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 38.6%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +258	deep intronic (+258 nt into the intron)
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP -0.11	GERP 0.13, phastCons 0.004
Overall
CADD	3.986	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	AluJr sine, simple repeat · ambiguous alignment · confidence, not pathogenicity

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 38.6% European (non-Finnish) · 19,897/51,494 alleles

Filtering AF 38.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 38%

Overall 29.8% 31,959/107,138 alleles · common

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	51.8%	2
Amishnot grpmax-eligible	42.7%	2
European (non-Finnish)grpmax	38.6%	3
South Asian	38.3%	3
Admixed American	36%	3
Ashkenazi Jewishnot grpmax-eligible	29.7%	3
Remaining individualsnot grpmax-eligible	26.9%	4
Middle Eastern	22.6%	4
East Asian	16.1%	6
African / African-American	9.58%	10

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ABCD4
Coding: c.1636+258del
MANE Select: NM_005050
dbSNP: rs67310859
Type: Deletion
Location: chr14:74287552 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.18 · 4 PDB

Full ABCD4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCD4 p.Ala237fs Likely pathogenic ★★ same type
ABCD4 p.Trp377fs Pathogenic ★★ same type
ABCD4 c.669-11_669-8del Benign ★★ same type
ABCD4 p.Arg125fs Pathogenic ★ same type
ABCD4 p.Arg432fs Pathogenic ★ same type
ABCD4 p.Gln101fs Likely pathogenic ★ same type
ABCD4 p.Gln215fs Pathogenic ★ same type
ABCD4 p.Gly183_Trp184insTer 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/abcd4-c-1636-plus-258del (accessed [today's date]).

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