Is ABCC9 p.Thr336= (c.1008T>C) pathogenic?

ABCC9 p.Thr336= (c.1008T>C) is classified Conflicting classifications of pathogenicity in ABCC9 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-02-24). Very rare (popmax 0.0011%, sas); Associated with hypertrichotic osteochondrodysplasia Cantu type.

What condition is associated with ABCC9 p.Thr336= (c.1008T>C)?

ABCC9 p.Thr336= (c.1008T>C) is associated with hypertrichotic osteochondrodysplasia Cantu type, dilated cardiomyopathy 1O (ClinVar).

How common is ABCC9 p.Thr336= (c.1008T>C) in the general population?

ABCC9 p.Thr336= (c.1008T>C) is very rare (popmax 0.0011%, sas) (gnomAD).

ABCC9 p.Thr336=

c.1008T>C · rs778283866 · VCV882669

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

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 -1.5	GERP -2.8
Overall
CADD	6.32	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,056 alleles

Overall 0.000137% 2/1,460,932 alleles · very rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0016%	62,462
South Asiangrpmax	0.0011%	91,056

Remaining individuals shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Thr336=
Coding: c.1008T>C
MANE Select: NM_020297
dbSNP: rs778283866
Type: single nucleotide variant
Location: chr12:21912875 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.72
Residue 336: the abc transmembrane type-1 1 domain

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: dilated cardiomyopathy 1O

Similar variants

ABCC9 p.Thr336Ala 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-thr336 (accessed [today's date]).

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