Is ABCC9 p.Arg620Gln (c.1859G>A) pathogenic?

ABCC9 p.Arg620Gln (c.1859G>A) is classified Conflicting classifications of pathogenicity in ABCC9 (ClinVar, Conflicting submitters, 6 submitters; last evaluated 2025-11-09). AlphaMissense: likely benign (0.1628); Very rare (popmax 0.00334%, amr); Associated with Cardiovascular phenotype.

What condition is associated with ABCC9 p.Arg620Gln (c.1859G>A)?

ABCC9 p.Arg620Gln (c.1859G>A) is associated with Cardiovascular phenotype, dilated cardiomyopathy 1O, familial dilated cardiomyopathy (ClinVar).

How common is ABCC9 p.Arg620Gln (c.1859G>A) in the general population?

ABCC9 p.Arg620Gln (c.1859G>A) is very rare (popmax 0.00334%, amr) (gnomAD).

What do computational predictors say about ABCC9 p.Arg620Gln (c.1859G>A)?

AlphaMissense predicts likely benign (score 0.1628) — an in-silico prediction, not a clinical call.

ABCC9 p.Arg620Gln

c.1859G>A · rs139539832 · VCV520507

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 6 submitters

AlphaMissense

likely benign

0.1628 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00334%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Cardiovascular phenotype

Computational evidence

Protein change
AlphaMissense	0.1628	likely benign
REVEL	0.414	indeterminate
SaProt	LLR -6.09	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.9	GERP 1.7, phastCons 0.9
Regional constraint	o/e 0.79	unconstrained · MANE · 45 kb · p 0.00018 · regional, not allelic
Overall
CADD	23.4	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 0.00334% Admixed American · 2/59,914 alleles

Filtering AF 0.00208% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00183%

Overall 0.00254% 41/1,613,438 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00334%	29,957
Remaining individualsnot grpmax-eligible	0.0032%	31,243
European (non-Finnish)	0.00288%	34,692
African / African-American	0.00267%	37,495
South Asian	0.0011%	91,064

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: ABCC9
Protein: p.Arg620Gln
Coding: c.1859G>A
MANE Select: NM_020297
dbSNP: rs139539832
Type: single nucleotide variant
Location: chr12:21887878 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.72

Full ABCC9 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Cardiovascular phenotype — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: dilated cardiomyopathy 1O familial dilated cardiomyopathy

Similar variants

ABCC9 p.Arg620Leu Uncertain significance ★★ same residue
ABCC9 p.Arg620= Likely benign ★★ same residue
ABCC9 p.Arg620Pro Uncertain significance ★ ⚠ same residue
ABCC9 p.Arg620Ter Conflicting classifications of pathogenicity ★ same residue
ABCC9 c.2506-1G>A Pathogenic/Likely pathogenic ★★ same condition
ABCC9 p.Arg1116Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCC9 p.Arg1116His Pathogenic ★★ ⚠ same condition
ABCC9 p.Arg1154Gln Pathogenic ★★ ⚠ 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/abcc9-p-arg620gln (accessed [today's date]).

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