Is DPH2 p.Arg282fs (c.844del) pathogenic?

DPH2 p.Arg282fs (c.844del) is classified Conflicting classifications of pathogenicity in DPH2 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-12-02). Very rare (popmax 0.00266%, afr); Associated with developmental delay with short stature, dysmorphic facial features, and sparse hair 2.

How common is DPH2 p.Arg282fs (c.844del) in the general population?

DPH2 p.Arg282fs (c.844del) is very rare (popmax 0.00266%, afr) (gnomAD).

DPH2 p.Arg282fs

Q: What condition is associated with DPH2 p.Arg282fs (c.844del)?

DPH2 p.Arg282fs (c.844del) is associated with developmental delay with short stature, dysmorphic facial features, and sparse hair 2 (ClinVar).

c.844del · rs1557642000 · VCV3065569

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00266%, afr)

Conditions

developmental delay with short stature, dysmorphic facial features, and sparse hair 2

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 4 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 12	GERP 1.6, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00266% African / African-American · 2/75,066 alleles

Filtering AF 0.000442% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000166%

Overall 0.000206% 3/1,458,070 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00266%	37,533
Remaining individualsnot grpmax-eligible	0.0016%	62,452

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: DPH2
Protein: p.Arg282fs
Coding: c.844del
MANE Select: NM_001384
dbSNP: rs1557642000
Type: Deletion
Location: chr1:43971744 (GRCh38)
Gene constraint: LOEUF 0.914 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 83.60

Full DPH2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

developmental delay with short stature, dysmorphic facial features, and sparse hair 2 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DPH2 p.Arg282Leu Uncertain significance ★ ⚠ same residue
DPH2 p.Arg282His Likely benign ★ ⚠ same residue
DPH2 p.Arg477Ter Likely pathogenic ★ same condition
DPH2 p.Ser75Ter Likely pathogenic ★ same condition
DPH2 p.Arg201Cys Uncertain significance ★ same condition
DPH2 p.Gln308Ter 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/dph2-p-arg282fs (accessed [today's date]).

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