Is ARCN1 p.Asp334fs (c.1001dup) pathogenic?

ARCN1 p.Asp334fs (c.1001dup) is classified Pathogenic in ARCN1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2022-09-06). Absent from gnomAD; Associated with short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay.

How common is ARCN1 p.Asp334fs (c.1001dup) in the general population?

ARCN1 p.Asp334fs (c.1001dup) is absent from gnomAD (gnomAD).

ARCN1 p.Asp334fs

Q: What condition is associated with ARCN1 p.Asp334fs (c.1001dup)?

ARCN1 p.Asp334fs (c.1001dup) is associated with short stature, rhizomelic, with microcephaly, micrognathia, and developmental delay (ClinVar).

c.1001dup · rs2497713595 · VCV1704218

Pathogenic No assertion criteria

Classification

Pathogenic

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Not reported

no gnomAD frequency available for this variant

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 7 of 10
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 9.9	GERP 1.7, phastCons 1

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

Population frequency

dbSNP / gnomAD

No gnomAD frequency available for this variant. This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: ARCN1
Protein: p.Asp334fs
Coding: c.1001dup
MANE Select: NM_001655
dbSNP: rs2497713595
Type: Duplication
Location: chr11:118592724 (GRCh38)
Gene constraint: LOEUF 0.145 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 84.25
Residue 334: the mhd domain

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.Asp334= Likely benign ★★ same residue
ARCN1 p.Arg145fs Pathogenic ★ same condition
ARCN1 p.Glu296fs Pathogenic ★ same condition
ARCN1 p.Tyr56Ter Pathogenic ★ same condition
ARCN1 p.Leu127fs 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

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-asp334fs (accessed [today's date]).

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