Is ABCC9 p.Asp616= (c.1848C>T) pathogenic?

ABCC9 p.Asp616= (c.1848C>T) is classified Benign/Likely benign in ABCC9 (ClinVar, Multiple submitters, 13 submitters; last evaluated 2026-02-03). Low-frequency (popmax 4.89%, afr); Associated with hypertrichotic osteochondrodysplasia Cantu type.

What condition is associated with ABCC9 p.Asp616= (c.1848C>T)?

ABCC9 p.Asp616= (c.1848C>T) is associated with hypertrichotic osteochondrodysplasia Cantu type, cardiomyopathy, dilated cardiomyopathy 1O (ClinVar).

How common is ABCC9 p.Asp616= (c.1848C>T) in the general population?

ABCC9 p.Asp616= (c.1848C>T) is low-frequency (popmax 4.89%, afr) (gnomAD).

ABCC9 p.Asp616=

c.1848C>T · rs61001398 · VCV45391

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 13 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.89%, afr)

Conditions

hypertrichotic osteochondrodysplasia Cantu type

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.8	GERP -3.4
Overall
CADD	5.631	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.89% African / African-American · 3,662/74,928 alleles

Filtering AF 4.76% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.7%

Overall 0.267% 4,308/1,613,320 alleles · low-frequency

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.89%	20
Remaining individualsnot grpmax-eligible	0.391%	256
Middle Eastern	0.281%	356
Admixed American	0.277%	361
East Asian	0.0825%	1,212
South Asian	0.0176%	5,692
European (non-Finnish)	0.0141%	7,106

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.Asp616=
Coding: c.1848C>T
MANE Select: NM_020297
dbSNP: rs61001398
Type: single nucleotide variant
Location: chr12:21887889 (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

hypertrichotic osteochondrodysplasia Cantu type — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: cardiomyopathy dilated cardiomyopathy 1O atrial fibrillation, familial, 12 intellectual disability and myopathy syndrome

Similar variants

ABCC9 p.Asp616Asn Uncertain significance ★ ⚠ 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
ABCC9 p.Arg1154Trp Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCC9 p.Gln852Ter Pathogenic/Likely pathogenic ★★ same condition
ABCC9 p.Gly989Glu Pathogenic/Likely 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-asp616 (accessed [today's date]).

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