Is ABCA12 p.Gln554Arg (c.1661A>G) pathogenic?

ABCA12 p.Gln554Arg (c.1661A>G) is classified Conflicting classifications of pathogenicity in ABCA12 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2023-03-01). AlphaMissense: likely benign (0.079); Very rare (popmax 0.00667%, amr); Associated with Inborn genetic diseases.

What condition is associated with ABCA12 p.Gln554Arg (c.1661A>G)?

ABCA12 p.Gln554Arg (c.1661A>G) is associated with Inborn genetic diseases (ClinVar).

How common is ABCA12 p.Gln554Arg (c.1661A>G) in the general population?

ABCA12 p.Gln554Arg (c.1661A>G) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about ABCA12 p.Gln554Arg (c.1661A>G)?

AlphaMissense predicts likely benign (score 0.079) — an in-silico prediction, not a clinical call.

ABCA12 p.Gln554Arg

c.1661A>G · rs778200334 · VCV2492829

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.079 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.079	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -4.06	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 2.4	GERP -0.26, phastCons 1
Regional constraint	o/e 1.03	unconstrained · MANE · 94 kb · p 0.48 · regional, not allelic
Overall
CADD	15.34	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 0.00667% Admixed American · 4/59,950 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000274% 4/1,460,216 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: ABCA12
Protein: p.Gln554Arg
Coding: c.1661A>G
MANE Select: NM_173076
dbSNP: rs778200334
Type: single nucleotide variant
Location: chr2:215018129 (GRCh38)
Gene constraint: LOEUF 0.582 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.32
Residue 554: a UniProt-annotated variant site (in arci4b)

Full ABCA12 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

ABCA12 p.Gln554Ter Likely pathogenic ★ same residue
ABCA12 p.Gln554= Benign ★ same residue
ABCA12 p.Ala134Ser Uncertain significance ★★ ⚠ same condition
ABCA12 p.Ala51Glu Uncertain significance ★★ ⚠ same condition
ABCA12 p.Ala833Val Uncertain significance ★★ ⚠ same condition
ABCA12 p.Arg1417Trp Uncertain significance ★★ ⚠ same condition
ABCA12 p.Arg1950Gln Uncertain significance ★★ ⚠ same condition
ABCA12 p.Asp505Val 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/abca12-p-gln554arg (accessed [today's date]).

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