Is ABCC6 p.Val354Phe (c.1060_1062delinsTTT) pathogenic?

ABCC6 p.Val354Phe (c.10601062delinsTTT) is classified Uncertain significance in ABCC6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-26). Associated with pseudoxanthoma elasticum, forme fruste.

What condition is associated with ABCC6 p.Val354Phe (c.1060_1062delinsTTT)?

ABCC6 p.Val354Phe (c.1060_1062delinsTTT) is associated with pseudoxanthoma elasticum, forme fruste, autosomal recessive inherited pseudoxanthoma elasticum, arterial calcification, generalized, of infancy, 2 (ClinVar).

ABCC6 p.Val354Phe

c.1060_1062delinsTTT · VCV3578596

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

Conditions

pseudoxanthoma elasticum, forme fruste

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.21	GERP 0.055, phastCons 0.007
Regional constraint	o/e 0.98	unconstrained · MANE · 59 kb · p 0.39 · regional, not allelic
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Variant & gene context

Gene: ABCC6
Protein: p.Val354Phe
Coding: c.1060_1062delinsTTT
MANE Select: NM_001171
Type: Indel
Location: chr16:16202115 (GRCh38)
Gene constraint: LOEUF 0.917 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.32 · 4 PDB
Residue 354: the abc transmembrane type-1 1 domain

Full ABCC6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

pseudoxanthoma elasticum, forme fruste — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: autosomal recessive inherited pseudoxanthoma elasticum arterial calcification, generalized, of infancy, 2

Similar variants

ABCC6 p.Val354Met Conflicting classifications of pathogenicity ★ ⚠ same residue
ABCC6 p.Asn411Ser Uncertain significance ★★ same condition
ABCC6 c.341_345+8delinsG Pathogenic ★ same condition
ABCC6 p.Gln703Glu Uncertain significance ★ same condition
ABCC6 p.Ser245Glu Uncertain significance ★ same condition
ABCC6 p.Asn578fs Likely pathogenic same condition
ABCC6 c.3307-38_3307-3delinsAGA Uncertain significance same condition
ABCC6 c.1868-5T>G 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/abcc6-p-val354phe (accessed [today's date]).

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