Is ABCA2 p.Arg1438Gly (c.4312C>G) pathogenic?

ABCA2 p.Arg1438Gly (c.4312C>G) is classified Uncertain significance in ABCA2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-09). AlphaMissense: ambiguous (0.3554); Absent from gnomAD v4.1.

How common is ABCA2 p.Arg1438Gly (c.4312C>G) in the general population?

ABCA2 p.Arg1438Gly (c.4312C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCA2 p.Arg1438Gly (c.4312C>G)?

AlphaMissense predicts ambiguous (score 0.3554) — an in-silico prediction, not a clinical call.

ABCA2 p.Arg1438Gly

c.4312C>G · VCV3847695

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3554 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.3554	ambiguous
REVEL	0.597	indeterminate
SaProt	LLR -9.48	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.53 · evaluated, not missing
Constraint at this position
Conservation	phyloP 9.6	GERP -1.5, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 515 bp · p 6.9e-05 · regional, not allelic
Overall
CADD	23.0	PHRED · no single calibrated threshold — expert panels disagree

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM R1437G vs ClinVar R1438G) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: ABCA2
Protein: p.Arg1438Gly
Coding: c.4312C>G
MANE Select: NM_001606
Type: single nucleotide variant
Location: chr9:137013967 (GRCh38)
Gene constraint: LOEUF 0.436 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 71.46
Residue 1438: a UniProt-annotated variant site (in idpogsa)

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

Similar variants

ABCA2 p.Arg1438Cys Uncertain significance ★ ⚠ same residue
ABCA2 p.Arg1438His Uncertain significance ★ same residue
ABCA2 p.Gln1370Ter Likely pathogenic ★★ same type
ABCA2 c.3883-3C>T Uncertain significance ★★ same type
ABCA2 p.Ala1357Thr Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1620Thr Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1645Val Uncertain significance ★★ ⚠ same type
ABCA2 p.Ala1715Ser Uncertain significance ★★ ⚠ 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/abca2-p-arg1438gly (accessed [today's date]).

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