Is ABCA5 p.Ile583Val (c.1747A>G) pathogenic?

ABCA5 p.Ile583Val (c.1747A>G) is classified Uncertain significance in ABCA5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-05). AlphaMissense: likely benign (0.0671); Very rare (popmax 0.00335%, amr).

How common is ABCA5 p.Ile583Val (c.1747A>G) in the general population?

ABCA5 p.Ile583Val (c.1747A>G) is very rare (popmax 0.00335%, amr) (gnomAD).

What do computational predictors say about ABCA5 p.Ile583Val (c.1747A>G)?

AlphaMissense predicts likely benign (score 0.0671) — an in-silico prediction, not a clinical call.

ABCA5 p.Ile583Val

c.1747A>G · rs2075506207 · VCV2544628

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0671 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00335%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0671	likely benign
REVEL	0.035	moderately benign-leaning
SaProt	LLR -8.74	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.6	GERP 0.69, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.22 · regional, not allelic
Overall
CADD	17.16	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00335% Admixed American · 2/59,732 alleles

Filtering AF 0.000555% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000208%

Overall 0.000274% 4/1,459,144 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00335%	29,866
Finnishnot grpmax-eligible	0.00158%	63,322
South Asian	0.0011%	90,840

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: ABCA5
Protein: p.Ile583Val
Coding: c.1747A>G
MANE Select: NM_172232
dbSNP: rs2075506207
Type: single nucleotide variant
Location: chr17:69289897 (GRCh38)
Gene constraint: LOEUF 0.97 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.12
Residue 583: the abc transporter 1 domain

Full ABCA5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ABCA5 p.Ser288Phe Uncertain significance ★★ ⚠ same type
ABCA5 c.4765+3A>G Likely benign ★★ same type
ABCA5 p.Asn190Ser Likely benign ★★ ⚠ same type
ABCA5 p.Asn768Asp Benign ★★ same type
ABCA5 p.Asp817Tyr Likely benign ★★ ⚠ same type
ABCA5 p.Gly1159Arg Likely benign ★★ ⚠ same type
ABCA5 p.Gly128= Benign/Likely benign ★★ same type
ABCA5 p.Ile1173Val Likely benign ★★ 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/abca5-p-ile583val (accessed [today's date]).

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