Is ABCA2 p.Val1730Ile (c.5188G>A) pathogenic?

ABCA2 p.Val1730Ile (c.5188G>A) is classified Uncertain significance in ABCA2 (ClinVar, Multiple submitters, 4 submitters; last evaluated 2024-04-04). AlphaMissense: likely benign (0.1657); Ultra-rare (popmax 0.0787%, afr); Associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia.

How common is ABCA2 p.Val1730Ile (c.5188G>A) in the general population?

ABCA2 p.Val1730Ile (c.5188G>A) is ultra-rare (popmax 0.0787%, afr) (gnomAD).

What do computational predictors say about ABCA2 p.Val1730Ile (c.5188G>A)?

AlphaMissense predicts likely benign (score 0.1657) — an in-silico prediction, not a clinical call.

ABCA2 p.Val1730Ile

Q: What condition is associated with ABCA2 p.Val1730Ile (c.5188G>A)?

ABCA2 p.Val1730Ile (c.5188G>A) is associated with intellectual developmental disorder with poor growth and with or without seizures or ataxia (ClinVar).

c.5188G>A · rs192038143 · VCV1878717

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1657 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0787%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

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

Computational evidence

Protein change
AlphaMissense	0.1657	likely benign
REVEL	0.384	indeterminate
SaProt	LLR -6.18	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.26 · evaluated, not missing
Constraint at this position
Conservation	phyloP 3.1	GERP 0.47, phastCons 1
Regional constraint	o/e 0.67	unconstrained · MANE · 3,800 bp · p 6.1e-23 · regional, not allelic
Overall
CADD	25.7	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM V1729I vs ClinVar V1730I) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0787% African / African-American · 59/74,996 alleles

Filtering AF 0.0626% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0568%

Overall 0.0131% 211/1,611,988 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0787%	1,271
Middle Eastern	0.066%	1,514
Admixed American	0.03%	3,333
South Asian	0.0297%	3,372
Remaining individualsnot grpmax-eligible	0.0128%	7,806
European (non-Finnish)	0.00805%	12,416

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
Protein: p.Val1730Ile
Coding: c.5188G>A
MANE Select: NM_001606
dbSNP: rs192038143
Type: single nucleotide variant
Location: chr9:137012376 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 1730: a UniProt-annotated variant site (in idpogsa)

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-p-val1730ile (accessed [today's date]).

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