Is ABCA2 c.678+6G>A pathogenic?

ABCA2 c.678+6G>A is classified Uncertain significance in ABCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-17). Very rare (popmax 0.00801%, sas); Associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia.

How common is ABCA2 c.678+6G>A in the general population?

ABCA2 c.678+6G>A is very rare (popmax 0.00801%, sas) (gnomAD).

ABCA2 c.678+6G>A

Q: What condition is associated with ABCA2 c.678+6G>A?

ABCA2 c.678+6G>A is associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia (ClinVar).

VCV4850084

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00801%, sas)

Conditions

intellectual developmental disorder with poor growth and with or without seizures or ataxia

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
Splice region	donor +6	donor splice region (+6, within the first 6 intronic nt) · inside the BP7-excluded zone
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.27	GERP 0.084, phastCons 0.002
Non-coding constraint	Z 6.05	1 kb window · o/e 0.67 · regional · uncalibrated
Overall
CADD	4.62	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00801% South Asian · 7/87,400 alleles

Filtering AF 0.00372% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00263%

Overall 0.000488% 7/1,434,180 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: ABCA2
Coding: c.678+6G>A
MANE Select: NM_001606
Type: single nucleotide variant
Location: chr9:137021885 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46

Full ABCA2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

intellectual developmental disorder with poor growth and with or without seizures or ataxia — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ABCA2 p.Gln1370Ter Likely pathogenic ★★ same condition
ABCA2 p.Ala367Thr Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg114Gln Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg1160His Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg1383His Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg1664Trp Uncertain significance ★★ ⚠ same condition
ABCA2 p.Arg954His Uncertain significance ★★ ⚠ same condition
ABCA2 p.Asn1755Lys 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/abca2-c-678-plus-6g-a (accessed [today's date]).

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