Is ABCD4 p.His342Gln (c.1026C>A) pathogenic?

ABCD4 p.His342Gln (c.1026C>A) is classified Uncertain significance in ABCD4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-02-05). AlphaMissense: likely pathogenic (0.8251); Very rare (popmax 0.000137%); Associated with Inborn genetic diseases.

What condition is associated with ABCD4 p.His342Gln (c.1026C>A)?

ABCD4 p.His342Gln (c.1026C>A) is associated with Inborn genetic diseases (ClinVar).

How common is ABCD4 p.His342Gln (c.1026C>A) in the general population?

ABCD4 p.His342Gln (c.1026C>A) is very rare (popmax 0.000137%) (gnomAD).

What do computational predictors say about ABCD4 p.His342Gln (c.1026C>A)?

AlphaMissense predicts likely pathogenic (score 0.8251) — an in-silico prediction, not a clinical call.

ABCD4 p.His342Gln

c.1026C>A · rs367709858 · VCV3129196

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8251 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000137%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8251	likely pathogenic
REVEL	0.733	pathogenic-leaning
SaProt	LLR -8.79	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.2	GERP 2.5, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 16 kb · p 0.79 · regional, not allelic
Overall
CADD	27.6	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 0.000137%

Overall 0.000137% 2/1,461,604 alleles · very rare

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.His342Gln
Coding: c.1026C>A
MANE Select: NM_005050
dbSNP: rs367709858
Type: single nucleotide variant
Location: chr14:74292553 (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

Disease context

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

Similar variants

ABCD4 p.His342Arg Uncertain significance ★ ⚠ same residue
ABCD4 p.Arg127Cys Uncertain significance ★★ ⚠ same condition
ABCD4 p.Arg252Gly Uncertain significance ★★ ⚠ same condition
ABCD4 p.Arg391Gln Uncertain significance ★★ ⚠ same condition
ABCD4 p.Arg442Gln Uncertain significance ★★ ⚠ same condition
ABCD4 p.Gln215Arg Uncertain significance ★★ ⚠ same condition
ABCD4 p.Gln446Arg Uncertain significance ★★ ⚠ same condition
ABCD4 p.Gly566Ser Uncertain significance ★★ ⚠ 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/abcd4-p-his342gln (accessed [today's date]).

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