Is ARCN1 p.Ala155fs (c.462del) pathogenic?

ARCN1 p.Ala155fs (c.462del) is classified Pathogenic in ARCN1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-30). Associated with short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay.

ARCN1 p.Ala155fs

Q: What condition is associated with ARCN1 p.Ala155fs (c.462del)?

ARCN1 p.Ala155fs (c.462del) is associated with short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay (ClinVar).

c.462del · VCV4531787

Pathogenic Single submitter

Classification

Pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

Conditions

short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function in a haploinsufficient gene (ClinGen)
NMD	predicted	premature termination codon in exon 4 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.3	GERP 1.7, phastCons 1

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Variant & gene context

Gene: ARCN1
Protein: p.Ala155fs
Coding: c.462del
MANE Select: NM_001655
Type: Deletion
Location: chr11:118583822 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.25

Full ARCN1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ARCN1 p.Tyr429fs Pathogenic ★ same condition
ARCN1 p.Val212fs Pathogenic same condition
ARCN1 c.654-15A>G Pathogenic/Likely pathogenic ★★ same condition
ARCN1 p.Arg170Ter Pathogenic ★★ same condition
ARCN1 p.Arg312Ter Pathogenic ★★ same condition
ARCN1 p.Glu78del Likely pathogenic ★★ same condition
ARCN1 p.Arg314His Uncertain significance ★★ ⚠ same condition
ARCN1 p.Asp426Asn 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/arcn1-p-ala155fs (accessed [today's date]).

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