Is ABCA5 p.Gln484Arg (c.1451A>G) pathogenic?

ABCA5 p.Gln484Arg (c.1451A>G) is classified Benign in ABCA5 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-03-06). AlphaMissense: likely benign (0.0729); Common (popmax 22.6%, afr) — too common for a highly-penetrant pathogenic allele; Associated with ABCA5-related disorder.

What condition is associated with ABCA5 p.Gln484Arg (c.1451A>G)?

ABCA5 p.Gln484Arg (c.1451A>G) is associated with ABCA5-related disorder (ClinVar).

What do computational predictors say about ABCA5 p.Gln484Arg (c.1451A>G)?

AlphaMissense predicts likely benign (score 0.0729) — an in-silico prediction, not a clinical call.

ABCA5 p.Gln484Arg

Q: How common is ABCA5 p.Gln484Arg (c.1451A>G) in the general population?

ABCA5 p.Gln484Arg (c.1451A>G) is common (popmax 22.6%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1451A>G · rs17686569 · VCV3059440

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0729 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 22.6%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

ABCA5-related disorder

Computational evidence

Protein change
AlphaMissense	0.0729	likely benign
REVEL	0.056	moderately benign-leaning
SaProt	LLR -5.50	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 7.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 67 kb · p 0.22 · regional, not allelic
Overall
CADD	20.4	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 22.6% African / African-American · 16,840/74,504 alleles

Filtering AF 22.3% ClinGen BA1/BS1 input FAF95, joint · FAF99 22.2%

Overall 14% 224,232/1,597,538 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	22.6%	4
Admixed American	16.6%	6
European (non-Finnish)	14.2%	7
Remaining individualsnot grpmax-eligible	14.1%	7
Middle Eastern	14.1%	7
Finnishnot grpmax-eligible	13.8%	7
Ashkenazi Jewishnot grpmax-eligible	13.3%	8
South Asian	9.58%	10
Amishnot grpmax-eligible	4.61%	22
East Asian	3.3%	30

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.Gln484Arg
Coding: c.1451A>G
MANE Select: NM_172232
dbSNP: rs17686569
Type: single nucleotide variant
Location: chr17:69294699 (GRCh38)
Gene constraint: LOEUF 0.97 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.12
Residue 484: the abc transporter 1 domain; a UniProt-annotated variant site (in)

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

Disease context

ABCA5-related disorder

Similar variants

ABCA5 c.4415+3G>A Likely benign same condition
ABCA5 c.788+8A>C Likely benign same condition
ABCA5 p.Ala1444= Likely benign same condition
ABCA5 p.Ala178Thr Benign ⚠ same condition
ABCA5 p.Arg555= Likely benign same condition
ABCA5 p.Leu1131= Benign same condition
ABCA5 p.Leu1183= Benign same condition
ABCA5 p.Thr1248Met Likely benign 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/abca5-p-gln484arg (accessed [today's date]).

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