Is ABCD4 p.Leu569= (c.1705C>T) pathogenic?

ABCD4 p.Leu569= (c.1705C>T) is classified Likely benign in ABCD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2016-03-25). Very rare (popmax 0.00133%, afr).

How common is ABCD4 p.Leu569= (c.1705C>T) in the general population?

ABCD4 p.Leu569= (c.1705C>T) is very rare (popmax 0.00133%, afr) (gnomAD).

ABCD4 p.Leu569=

c.1705C>T · rs1057521999 · VCV384578

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00133%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.3, phastCons 1
Overall
CADD	11.36	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00133% African / African-American · 1/74,936 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.000991% 16/1,614,004 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,486
African / African-Americangrpmax	0.00133%	74,936
European (non-Finnish)	0.00119%	84,289

Remaining individuals 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
Protein: p.Leu569=
Coding: c.1705C>T
MANE Select: NM_005050
dbSNP: rs1057521999
Type: single nucleotide variant
Location: chr14:74286748 (GRCh38)
Gene constraint: LOEUF 0.772 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.18 · 4 PDB
Residue 569: the abc transporter domain

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

Similar variants

ABCD4 c.542+1G>T Pathogenic ★★ same type
ABCD4 p.Arg432Gln Likely pathogenic ★★ same type
ABCD4 p.Asn141Lys Pathogenic/Likely pathogenic ★★ same type
ABCD4 p.Gln530Ter Pathogenic/Likely pathogenic ★★ same type
ABCD4 p.Tyr176Ter Pathogenic/Likely pathogenic ★★ same type
ABCD4 c.1028+5G>A Uncertain significance ★★ same type
ABCD4 c.425+6C>T Uncertain significance ★★ same type
ABCD4 c.719+6T>C Uncertain significance ★★ 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-p-leu569 (accessed [today's date]).

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