Is ABCC9 p.Ala478Val (c.1433C>T) pathogenic?

ABCC9 p.Ala478Val (c.1433C>T) is classified Likely pathogenic in ABCC9 (ClinVar, Single submitter, 2 submitters; last evaluated 2025-05-28). AlphaMissense: likely pathogenic (0.6979); Absent from gnomAD v4.1; Associated with hypertrichotic osteochondrodysplasia Cantu type.

What condition is associated with ABCC9 p.Ala478Val (c.1433C>T)?

ABCC9 p.Ala478Val (c.1433C>T) is associated with hypertrichotic osteochondrodysplasia Cantu type (ClinVar).

How common is ABCC9 p.Ala478Val (c.1433C>T) in the general population?

ABCC9 p.Ala478Val (c.1433C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about ABCC9 p.Ala478Val (c.1433C>T)?

AlphaMissense predicts likely pathogenic (score 0.6979) — an in-silico prediction, not a clinical call.

ABCC9 p.Ala478Val

c.1433C>T · rs387907211 · VCV31949

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6979 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

hypertrichotic osteochondrodysplasia Cantu type

Computational evidence

Protein change
AlphaMissense	0.6979	likely pathogenic ✓ concordant with ClinVar
REVEL	0.793	moderately pathogenic-leaning
SaProt	LLR -7.67	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.17	constrained · MANE · 1,916 bp · p 9.7e-09 · regional, not allelic
Overall
CADD	29.6	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

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: ABCC9
Protein: p.Ala478Val
Coding: c.1433C>T
MANE Select: NM_020297
dbSNP: rs387907211
Type: single nucleotide variant
Location: chr12:21908099 (GRCh38)
Gene constraint: LOEUF 0.557 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.72
Residue 478: the abc transmembrane type-1 1 domain; a UniProt-annotated variant site (in htocd; rat abcc9 construct containing this mutation shows gain of function)

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

Similar variants

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.Gly989Glu Pathogenic/Likely pathogenic ★★ same condition
ABCC9 p.Thr1202Met Pathogenic/Likely pathogenic ★★ ⚠ same condition
ABCC9 c.1012-7G>A Uncertain significance ★★ same condition
ABCC9 c.3315+6T>C 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/abcc9-p-ala478val (accessed [today's date]).

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